Quantitative Proteomic Approach Reveals Altered Metabolic Pathways in Response to the Inhibition of Lysine Deacetylases in A549 Cells under Normoxia and Hypoxia

Growing evidence is showing that acetylation plays an essential role in cancer, but studies on the impact of KDAC inhibition (KDACi) on the metabolic profile are still in their infancy. Here, we analyzed, by using an iTRAQ-based quantitative proteomics approach, the changes in the proteome of KRAS-mutated non-small cell lung cancer (NSCLC) A549 cells in response to trichostatin-A (TSA) and nicotinamide (NAM) under normoxia and hypoxia. Part of this response was further validated by molecular and biochemical analyses and correlated with the proliferation rates, apoptotic cell death, and activation of ROS scavenging mechanisms in opposition to the ROS production. Despite the differences among the KDAC inhibitors, up-regulation of glycolysis, TCA cycle, oxidative phosphorylation and fatty acid synthesis emerged as a common metabolic response underlying KDACi. We also observed that some of the KDACi effects at metabolic levels are enhanced under hypoxia. Furthermore, we used a drug repositioning machine learning approach to list candidate metabolic therapeutic agents for KRAS mutated NSCLC. Together, these results allow us to better understand the metabolic regulations underlying KDACi in NSCLC, taking into account the microenvironment of tumors related to hypoxia, and bring new insights for the future rational design of new therapies.     

On the influence of gamma prime upon machining of advanced nickel based superalloy

Whilst gamma prime (γ′) phase is the strengthening phase in Ni-based superalloys its influence on machining has been seldom investigated. This paper reports for the first time on the effect of γ′ upon machining of Ni-based superalloys when cutting with parameters yielding different cutting temperature intervals which lead to strengthening/softening effects on the workpiece (sub)surface. In-depth XRD, SEM/FIB, EBSD analysis and unique micro-pillar testing in the workpiece superficial layers indicated that with the increase of γ′ fraction the grain plastic deformation significantly decreased, while specific cutting energy can switch from low to high values influenced by the real cutting temperature.     

Molecular Mechanisms of Fetal Tendon Regeneration Versus Adult Fibrous Repair

Tendinopathies are painful, disabling conditions that afflict 25% of the adult human population. Filling an unmet need for realistic large-animal models, we here present an ovine model of tendon injury for the comparative study of adult scarring repair and fetal regeneration. Complete regeneration of the fetal tendon within 28 days is demonstrated, while adult tendon defects remained macroscopically and histologically evident five months post-injury. In addition to a comprehensive histological assessment, proteome analyses of secretomes were performed. Confirming histological data, a specific and pronounced inflammation accompanied by activation of neutrophils in adult tendon defects was observed, corroborated by the significant up-regulation of pro-inflammatory factors, neutrophil attracting chemokines, the release of potentially tissue-damaging antimicrobial and extracellular matrix-degrading enzymes, and a response to oxidative stress. In contrast, secreted proteins of injured fetal tendons included proteins initiating the resolution of inflammation or promoting functional extracellular matrix production. These results demonstrate the power and relevance of our novel ovine fetal tendon regeneration model, which thus promises to accelerate research in the field. First insights from the model already support our molecular understanding of successful fetal tendon healing processes and may guide improved therapeutic strategies.     

Anteil erneuerbarer Energien und klimarelevante CO2-Emissionen aus der thermischen Verwertung von Abfällen in Österreich

Since combustible wastes usually consist of biogenic (e.g. paper, wood, food waste) and fossil organic matter (plastics), their thermal recovery results in climate neutral and climate relevant CO₂ emissions. Moreover, the fraction of biogenic materials in the waste feed is relevant for the amount of renewable energy produced. The latter has to be reported and might be subsidized according to national laws (e.g. based on European directive 2009/28/EG). The present study represents the first comprehensive evaluation of the share of biogenic and fossil materials in the waste feed of waste-to-energy (WTE) plants on a national basis. The Balance Method, which is patented on a European level by TU Wien, was applied to 10 out of 13 Austrian WTE plants (around 2.3 Mio tons of waste corresponding to around 88 % of the overall waste feed in Austrian WTE plants). The method is based on the mathematical reconciliation of the material properties (e.g. mean chemical composition of biogenic and fossil materials) and routinely recorded operating data of WTE plants (e.g. flue gas volume, CO₂ and O₂-content in the dry flue gas, steam production). The results demonstrate large variations for the share of energy from biogenic sources in the different WTE plants, ranging from 35.7 ± 2.4 % to 61.2 ± 2.7 % (based on annual averages). Additionally, for several WTE plants large temporal variations can be observed based on monthly mean values. Thus, a plant-specific and continuous evaluation of the waste composition in WTE plants (which the Balance Method allows to do at reasonable efforts) can be recommended for a reliable reporting of the renewable share of energy or fossil CO₂ emissions from waste incineration. The energy input which stems from fossil and biogenic sources can be estimated to 11,450 ± 120 TJ and 10,730 ± 110 TJ, respectively for the year 2014 (for the 10 WTE plants). In total 1060 ± 24 kt fossil CO₂ emissions from the thermal recovery of waste in Austria’s WTE plants in 2014 could be determined (estimation for all 13 WTE plants).     

Increased hydropower production and hydropeaking mitigation along the Upper Inn River (Tyrol,Austria) with a combination of buffer reservoirs,diversion hydropower plants and retention basins

Research on hydropeaking in Austria started in the 1990s and the implementation of the WFD stipulated large research projects since the year 2009. The first research projects supported the process understanding and in a second investigation step, measures were evaluated. The mountains in the region of Tyrol create large heads and thus support the production of flexible energy. In this region, TIWAG is operating 9 large (>10 MW) and 27 small (<10 MW) hydropower plants, with an installed capacity of about 1,550 MW and a mean annual production of 3,000 GWh. As the governmental energy strategy foresees an extension of the hydropower production in Austria, suitable options were selected in 2004 by TIWAG and the water management framework plan for Western Tyrol was developed. This strategic planning instrument proposes five large power plants, with a generation of 1,800 GWh/year of renewable energy, which enables to reach the WFD targets, because the concept includes hydropeaking mitigation by combining buffer reservoirs (impoundments), diversion hydropower plants, and retention basins. We present our promising concept of hydropeaking mitigation and exemplify this based on the GKI, a hydropeaking diversion hydropower plants (HPP) at the Swiss/Austrian border as well as the Silz hydropeaking retention basin, with a volume of about 300,000 m³. As the presented case studies are the largest measures for hydropeaking mitigation being currently implemented in Central Europe, they have pilot-character. Thus, ongoing research and monitoring programs are expected to improve the knowledge about hydropeaking mitigation.     

Factors structuring macroinvertebrate communities in a headwater stream and its springs in the Upper Austrian Limestone Alps

The Almbach, a headwater stream in the Upper Austrian foothills of the Alps bordered by mountain pastures was studied to gain insight into the benthic macroinvertebrate community and its habitat. Two springs, one of them fenced in to prevent livestock access, and two more sites of the headwater section were investigated. A discriminant analysis (DA) based on hydrochemistry and phytobenthos revealed three functions with 86% of all samples correctly classified to the four sites. The first function clearly separated the two springs with phosphorus and oxygen as the most important discriminating factors. Spring sites and headwater sites were split up by the second function mainly due to nitrate concentration, but no differences could be detected for the two stream sites. With the exception of the fenced spring, indicator taxa could be assigned to all sites by means of an Indicator Species Analysis (ISA). Polyvalent taxa groups such as Gastropoda and Ostracoda were indicators for the unfenced spring site. This is in accordance to observed low abundances of sensitive plecopteran taxa and suggests a negative impact of livestock trampling on the invertebrate community. Redundancy Analysis explained 99% of the macroinvertebrate‐environment relation. The first axis separated springs from stream sites and was correlated with nitrate, pH, water temperature and phytobenthos eveness. Phosphorus was responsible for splitting the unfenced spring and the downstream station from the fenced spring and the upstream location along the second axis. Ephemeropteran taxa like Habrophlebia sp. were related to elevated pH, increased water temperature and low nitrate concentrations. In accordance to the ISA, nitrate played an important role for tolerant Gastropoda and Ostracoda at the unfenced spring. Copyright © 2010 John Wiley & Sons, Ltd.     

Time Delay Estimation by Cross-covariance Maximization of Quadrature Sampled Narrowband Signals

A numerically efficient algorithm for estimating the time delay from observations of a stationary narrowband signal and its delayed version is investigated. Quadrature sampling, a variant of bunched sampling, is applied to estimate samples of the quadrature components of the cross-covariance function of the two signals. The baseband magnitude squared of this function can be maximized for time delay estimation. Because the time delay is unknown, the baseband cross-covariance function cannot be interpolated from the estimated samples. Numerical maximization of the samples' magnitude squared and quadratic interpolation, however, results in a reasonable time delay estimate.