Establishing a Markerless Genetic Exchange System for Methanosarcina mazei Strain Gö1 for Constructing Chromosomal Mutants of Small RNA Genes

A markerless genetic exchange system was successfully established in Methanosarcina mazei strain Gö1 using the hpt gene coding for hypoxanthine phosphoribosyltransferase. First, a chromosomal deletion mutant of the hpt gene was generated conferring resistance to the purine analog 8-aza-2,6-diaminopurine (8-ADP). The nonreplicating allelic exchange vector (pRS345) carrying the pac-resistance cassette for direct selection of chromosomal integration, and the hpt gene for counterselection was introduced into this strain. By a pop-in and ultimately pop-out event of the plasmid from the chromosome, allelic exchange is enabled. Using this system, we successfully generated a M. mazei deletion mutant of the gene encoding the regulatory non-coding RNA sRNA154. Characterizing M. mazeiΔsRNA154 under nitrogen limiting conditions demonstrated differential expression of at least three cytoplasmic proteins and reduced growth strongly arguing for a prominent role of sRNA154 in regulation of nitrogen fixation by posttranscriptional regulation

Immunotherapy of Peritoneal Carcinomatosis with the Antibody Catumaxomab in Colon, Gastric, or Pancreatic Cancer: An Open-Label, Multicenter, Phase I/II Trial

Background: Peritoneal carcinomatosis (PC) is common in gastrointestinal (GI) cancer and there is no effective standard treatment. We investigated the tolerability and maximum tolerated dose (MTD) of the trifunctional antibody catumaxomab in patients with PC. Methods: In this open-label, phase I/II clinical trial, patients with epithelial cell adhesion molecule (EpCAM)-positive PC from GI cancer received 4 sequential intraperitoneal catumaxomab infusions: day 0: 10 mu g; day 3: 10 or 20 mu g; day 7: 30, 50, or 100 mu g; and day 10: 50, 100, or 200 mu g. Dose escalation was guided by dose-limiting toxicities. Results: The MTD was 10, 20, 50, and 200 mu g on days 0, 3, 7, and 10, respectively. Catumaxomab had an acceptable safety profile: Most common treatment-related adverse events (at the MTD) were fever, vomiting, and abdominal pain. At final examination, 11/17 evaluable patients (65%) were progression free: 1 patient had a complete and 3 a partial response. Median overall survival from the time of diagnosis of PC was 502 days. Conclusions: Intraperitoneal catumaxomab is a promising option for the treatment of PC from GI cancer

A Quantum Optimization Case Study for a Transport Robot Scheduling Problem

We present a comprehensive case study comparing the performance of D-Waves' quantum-classical hybrid framework, Fujitsu's quantum-inspired digital annealer, and Gurobi's state-of-the-art classical solver in solving a transport robot scheduling problem. This problem originates from an industrially relevant real-world scenario. We provide three different models for our problem following different design philosophies. In our benchmark, we focus on the solution quality and end-to-end runtime of different model and solver combinations. We find promising results for the digital annealer and some opportunities for the hybrid quantum annealer in direct comparison with Gurobi. Our study provides insights into the workflow for solving an application-oriented optimization problem with different strategies, and can be useful for evaluating the strengths and weaknesses of different approaches

Tm3+/Ho3+ co-doped germanate glass and double-clad optical fiber for broadband emission and lasing above 2 μm

In this paper, a 2 μm broadband emission under 796 nm laser diode excitation in low phonon energy GeO2-Ga2O3-BaO glass system is co-doped with 0.7Tm2O3/(0.07-0.7)Ho2O3 (mol%). The widest emission band (where the Tm3+ → Ho3+ energy transfer efficiency is 63%) was obtained for 0.7Tm2O3/0.15Ho2O3 co-doped glass from which a double-clad optical fiber was realized and investigated. Optimization of Tm3+/Ho3+ concentration enabled the acquisition of broadband amplified spontaneous emission (ASE) in double-clad optical fiber with a full width at half maximum (FWHM): 377 nm and 662 nm for 3 dB and 10 dB bandwidth, respectively. ASE spectrum is a result of the superposition of (Tm3+: 3H4 →Η3F4) 1.45 μm, (Tm3+: 3F4 → 3H6) 1.8 μm and (Ho3+:5I7 → 5I8) 2 μm emission bands. Hence, highly rare-earth co-doped germanate glass is characterized by a remarkably broader ASE spectrum than silica and tellurite fibers showed promising lasing properties for their further application in tunable and dual wavelength lasers

Analysis of the dust evolution in the circumstellar disks of TTauri stars

We present a compositional analysis of 8-13um spectra of 32 young stellar objects (YSOs). Our sample consists of 5 intermediate-mass stars and 27 low-mass stars. While the spectra and first scientific results have already been published by Przygodda et al. (2003) and Kessler-Silacci et al. (2004) we perform a more detailed analysis of the 10um silicate feature. In our analysis we assume that this emission feature can be represented by a linear superposition of the wavelength-dependent opacity $\kappa_{\rm abs}(\lambda)$ describing the optical properties of silicate grains with different chemical composition, structure, and grain size. The determination of an adequate fitting equation is another goal of this study. Using a restricted number of fitting parameters we investigate which silicate species are necessary for the compositional fitting. Particles with radii of 0.1um- and 1.5um consisting of amorphous olivine and pyroxene, forsterite, enstatite, and quartz have been considered. Only compact, homogeneous dust grains have been used in the presented fitting procedures. In this context we show that acceptable fitting results can also be achieved if emission properties of porous silicate grains are considered instead. Although some previous studies give reasons for the similarity between the dust in circumstellar disks of TTauri stars and Herbig Ae/Be stars, a quantitative comparison has been missing, so far. Therefore, we conclude with a discussion of the results of a 10um spectroscopic survey of van Boekel et al. (2005) who focus on Herbig Ae/Be stars, the higher mass counterparts of T Tauri stars and draw comparisons to this and other studies. We find that the results of our study of T Tauri systems partly agree with previous studies of Herbig Ae/Be stars.Comment: 17 pages, 6 figure

Grain growth in the inner regions of Herbig Ae/Be star disks

We present new mid-infrared spectroscopy of the emission from warm circumstellar dust grains in Herbig Ae/Be stars. Our survey significantly extends the sample that was studied by Bouwman et al. (2001). We find a correlation between the strength of the silicate feature and its shape. We interpret this as evidence for the removal of small (0.1 mu m) grains from the disk surface while large (1-2 mu m) grains persist. If the evolution of the grain size distribution is dominated by gravitational settling, large grains are expected to disappear first, on a timescale which is much shorter than the typical age of our programme stars. Our observations thus suggest a continuous replenishment of micron sized grains at the disk surface. If the grain replenishment is due to the dredge-up of dust from the disk interior, the mineralogy we observe is representative of the bulk composition of dust in these stars. Based on observations obtained at the European Southern Observatory (ESO), La Silla, and on observations with ISO, an ESA project with instruments funded by ESA Member States (especially the PI countries: France, Germany, The Netherlands and the UK) and with the participation of ISAS and NASA

Ultrastable, high-repetition-rate attosecond beamline for time-resolved XUV-IR coincidence spectroscopy

The implementation of attosecond photoelectron-photoion coincidence spectroscopy for the investigation of atomic and molecular dynamics calls for a high-repetition-rate driving source combined with experimental setups characterized by excellent stability for data acquisition over time intervals ranging from a few hours up to a few days. This requirement is crucial for the investigation of processes characterized by low cross sections and for the characterization of fully differential photoelectron(s) and photoion(s) angular and energy distributions. We demonstrate that the implementation of industrial-grade lasers, combined with a careful design of the delay line implemented in the pump-probe setup, allows one to reach ultrastable experimental conditions leading to an error in the estimation of the time delays of only 12 as. This result opens new possibilities for the investigation of attosecond dynamics in simple quantum systems

Glass powder doping of nanocrystal-doped fibres: challenges and results

Incorporating new optical materials as nanocrystals into glass fibres for new functionalities has recently become a hot research topic. Our team (funded by the European FET Open project NCLAS) investigates the introduction of nanoscale laser crystallites into the core of optical fibres using the glass powder doping method. Active Y2O3:Pr3+ nanocrystals (NCs) were prepared via different synthesis methods, and structurally and spectroscopically characterized. After modification of technological parameters, the optimised NCs have been proposed as a luminescence centres to embed into germanate and silicate glass hosts. Glasses were analysed in terms of optical (transmission, refractive index matching to NCs) and thermal (thermal stability, viscosity, thermal expansion coefficient) parameters. Crystallisation issues during fibre drawing were particularly investigated. In a first step, glass powder-NCs mixing techniques and fibre preform preparation were developed. It was shown that temperature cycle profiles including dwell time and heating/cooling ramp rates influenced the glass-NCs properties and can lead to glass crystallisation or NCs dissolution. The sintering investigations pointed out the melting temperature limits to preserve active NCs in the glasses. In germanate glasses, Y2O3:Pr3+ dissolution was noticed at 800°C. In the case of the silicate glass compositions these regions vary from 700°C to 1050°C. The results allowed to select optical fibre drawing conditions performed by the powder-in-tube method. Their distribution uniformity is not yet sufficient, requiring further optimisation of the drawing kinetics.The research project funded by the European FET Open project NCLas: NanoCrystals in Fibre Lasers, Grant agreement number: 82916

Resolving the compact dusty discs around binary post-AGB stars using N-band interferometry

We present the first mid-IR long baseline interferometric observations of the circumstellar matter around binary post-AGB stars. Two objects, SX Cen and HD 52961, were observed using the VLTI/MIDI instrument during Science Demonstration Time. Both objects are known binaries for which a stable circumbinary disc is proposed to explain the SED characteristics. This is corroborated by our N-band spectrum showing a crystallinity fraction of more than 50 % for both objects, pointing to a stable environment where dust processing can occur. Surprisingly, the dust surrounding SX Cen is not resolved in the interferometric observations providing an upper limit of 11 mas (or 18 AU at the distance of this object) on the diameter of the dust emission. This confirms the very compact nature of its circumstellar environment. The dust emission around HD 52961 originates from a very small but resolved region, estimated to be ~ 35 mas at 8 micron and ~ 55 mas at 13 micron. These results confirm the disc interpretation of the SED of both stars. In HD 52961, the dust is not homogeneous in its chemical composition: the crystallinity is clearly concentrated in the hotter inner region. Whether this is a result of the formation process of the disc, or due to annealing during the long storage time in the disc is not clear.Comment: 12 pages, 10 figures, accepted for publication in A &