ARAconsult (Austria)

The leading first-in-class ruthenium-complex BOLD-100 currently undergoes clinical phase-II anticancer evaluation. Recently, BOLD-100 is identified as anti-Warburg compound. The present study shows that also deregulated lipid metabolism parameters characterize acquired BOLD-100-resistant colon and pancreatic carcinoma cells. Acute BOLD-100 treatment reduces lipid droplet contents of BOLD-100-sensitive but not -resistant cells. Despite enhanced glycolysis fueling lipid accumulation, BOLD-100-resistant cells reveal diminished lactate secretion based on monocarboxylate transporter 1 (MCT1) loss mediated by a frame-shift mutation in the MCT1 chaperone basigin. Glycolysis and lipid catabolism converge in the production of protein/histone acetylation substrate acetyl-coenzymeA (CoA). Mass spectrometric and nuclear magnetic resonance analyses uncover spontaneous cell-free BOLD-100-CoA adduct formation suggesting acetyl-CoA depletion as mechanism bridging BOLD-100-induced lipid metabolism alterations and histone acetylation-mediated gene expression deregulation. Indeed, BOLD-100 treatment decreases histone acetylation selectively in sensitive cells. Pharmacological targeting confirms histone de-acetylation as central mode-of-action of BOLD-100 and metabolic programs stabilizing histone acetylation as relevant Achilles' heel of acquired BOLD-100-resistant cell and xenograft models. Accordingly, histone gene expression changes also predict intrinsic BOLD-100 responsiveness. Summarizing, BOLD-100 is identified as epigenetically active substance acting via targeting several onco-metabolic pathways. Identification of the lipid metabolism as driver of acquired BOLD-100 resistance opens novel strategies to tackle therapy failure.

Primary sludge fermentate, a concentrated hydrolyzed wastewater carbon, was evaluated for use as an alternative carbon source for mainstream partial denitrification-anammox (PdNA) in a suspended growth activated sludge process in terms of partial denitrification (PdN) efficiency, PdNA nitrogen removal contributions, and final effluent quality. Fermenter operation at a 2-day sludge retention time (SRT) resulted in the maximum achievable yield of 0.14±0.05gsCOD/gVSS without release of excessive ammonia and phosphorus to the system. Based on the results of batch experiments, fermentate addition led to PdN efficiency of 93±14%, which was similar to acetate at a nitrate residual of 2-3mgN/L. In the pilot-scale mainstream deammonification reactor, PdN efficiency using fermentate was 49±24%, which was lower than acetate (66±24% during acetate period I and 70±21% during acetate period II), most probably due to lower nitrate and ammonium kinetics in the PdN zone. Methanol cost-saving potential for the application of PdNA as the main short-cut nitrogen pathway was estimated to be 30% to 55% depending on the PdN efficiency achieved. PRACTITIONER POINTS: Primary sludge fermentate was evaluated as an alternative carbon source for mainstream partial denitrification-anammox (PdNA). Fermenter operated at a 1 to 2 day SRT resulted in the maximum achievable yield without the release of excessive ammonia and phosphorus to the system. Although 93% partial denitrification efficiency was achieved with fermentate in batch experiments, around 49% PdN efficiency was achieved in pilot studies. Application of PdNA with fermentate can result in significant methanol cost savings.

This work is devoted to the efficient simulation of large multi-physical networks stemming from automated modeling processes in system simulation software. The simulation of hybrid, battery and fuel cell electric vehicle applications requires the coupling of electric, mechanic, fluid and thermal networks. Each network is established by combining the connection structure of a graph with physical equations of elementary components and resulting in a differential algebraic equation (DAE). In order to speed up the simulation a non-iterative multirate time integration co-simulation method for the system of coupled DAEs is established. The power of the multirate method is shown via two representative examples of a battery powered electric vehicle with a cooling system for the battery pack and a three phase inverter with a cooling system.

Abstract The connection between tunnels and cross passages places high demands on support and safety measures, especially for mechanized tunnelling with segmental lining. The critical task is to develop a temporary support system during the opening of the precast segmental lining until the inner lining of the cross passage has developed its full bearing capacity and is acting as a final support measure. For singleshell tunnels with waterproof linings, the serviceability of a durable waterproofing connection has to be ensured. A working group initiated by Austrian Federal Railways (ÖBB) has been concentrating on the opening of cross passages in TBM tunnels. The result of the research will be summarized in a guideline for the design of cross passage openings in tunnel with segmental lining. The guideline will describe the different systems already used for various scenarios according to the state of the technology. The paper summarizes the current state of the guideline and provides some recommended systems for lining support, waterproofing systems as well as some fundamental structural design models for the different support and coupling elements.

The thermal hydrolysis process (THP) is applied to enhance biogas production in anaerobic digestion (AD), reduce viscosity for improved mixing and dewatering and to reduce and sterilize cake solids. Large heat demands for steam production rely on dynamic effects like sludge throughput, gas availability and THP process parameters. Here, we propose a combined energy and process model suitable to describe the dynamic behaviour of THP in a full-plant context. The process model addresses interactions of THP with operational conditions covered by the AD model obeying mass continuity. Energy conservation is considered in balancing and converting various energy species dominated by thermal heat and calorific energy. The combined energy and process model was then applied on the THP at Blue Plains advanced WWTP (DC Water) to analyse the process and assess potential energy optimizations. It was found that dynamic effects like mismatched steam production and consumption, temporary gas shortages and underloaded units are responsible for energy inefficiencies with losses in electricity-production up to 29%.

METIS is the Mid-infrared Extremely large Telescope Imager and Spectrograph, one of the first generation instruments of ESO’s 39m ELT. All scientific observing modes of METIS require adaptive optics (AO) correction close to the diffraction limit. Demanding constraints are introduced by the foreseen coronagraphy modes, which require highest angular resolution and PSF stability. Further design drivers for METIS and its AO system are imposed by the wavelength regime: observations in the thermal infrared require an elaborate thermal, baffling and masking concept. METIS will be equipped with a Single-Conjugate Adaptive Optics (SCAO) system. An integral part of the instrument is the SCAO module. It will host a pyramid type wavefront sensor, operating in the near-IR and located inside the cryogenic environment of the METIS instrument. The wavefront control loop as well as secondary control tasks will be realized within the AO Control System, as part of the instrument. Its main actuators will be the adaptive quaternary mirror and the field stabilization mirror of the ELT. In this paper we report on the phase B design work for the METIS SCAO system; the opto-mechanical design of the SCAO module as well as the control loop concepts and analyses. Simulations were carried out to address a number of important aspects, such as the impact of the fragmented pupil of the ELT on wavefront reconstruction. The trade-off that led to the decision for a pyramid wavefront sensor will be explained, as well as the additional control tasks such as pupil stabilization and compensation of non-common path aberrations.

METIS, the Mid-nfrared E-ELT Imager and Spectrometer, will be providing high-sensitivity imaging and high-resolution spectroscopy in the mid-infrared (3-19 micrometer) to the E-ELT. In order to achieve the exceptional performance required by its driving science cases, exoplanets and proto-planetary disks, METIS will be featuring two Adaptive Optics (AO) systems — a first-light Single Conjugate Adaptive Optics (SCAO) system, complemented by a Laser Tomographic Adaptive Optics (LTAO) system, most likely, a few years after first light. METIS, being one of the three first light science instruments on the European Extremely Large Telescope (E-ELT), will be one of the first instruments using the integrated deformable mirror of the E-ELT for its Adaptive Optics (AO) correction. The internal SCAO system designed to maximize the performance for bright targets and has its wavefront sensors (WFSs) build inside the METIS cryostat to minimize the number of warm surfaces towards the science detectors. Although the internal dichroic will reflect all light short wards of 3 micrometers towards the WFS, only the IR light will most likely be used, mainly due to the expected improved performance at longer wavelengths for the WFS. A trade-off has been made between both visible versus infrared wave front sensing as well as Pyramid versus Shack-Hartmann, under various observing conditions and target geometries, taking into account performance, target availability, reliability and technology readiness level. The base line for the SCAO system is to minimize system complexity, thereby ensuring system availability and reliability even under first-light conditions. Since the SCAO system will require a bright guide star near the science target, it can only be used for a limited number of targets. The LTAO system, consisting of up to 6 LGS and up to 3 low-order NGS WFS and located outside the cryostat, is designed to increase the sky coverage on arbitrary targets to >80%. Investigations are ongoing if the internal SCAO system can be used as either a Low-Order WFS or metrology system.