Water Losses During Technical Snow Production: Results From Field Experiments

Alpine as well as Nordic skiing tourism strongly depend on the production of machine-made snow for the timely opening of the winter season. However, it is likely that sublimation, evaporation, wind drift, and the discharge of unfrozen water to the ground will result in the loss of significant parts of the water used. The relation between these water losses and the ambient meteorological conditions is poorly understood. We present results from a series of 12 detailed snow-making field tests performed in a ski resort near Davos, Switzerland. Water inflows, measured at the snow machine, are related to the mass of snow deposited on the ground. Snow amounts are calculated from accumulated volumes, measured with terrestrial laser scanning (TLS), and manually sampled snow densities. Additionally, samples of liquid water contents (LWCs) of the produced snow are presented. We find that 7 to 35 ± 7% (mean 21%) of the consumed water was lost during snow-making and that the loss is strongly related to the ambient meteorological conditions. Linear regression analysis shows that water losses increase with air temperature (TA). Combining our data with observations from earlier field measurements shows similar correlations

Interleukin-7 Induces Differential Lymphokine-Activated Killer Cell Activity Against Human Melanoma Cells, Keratinocytes, and Endothelial Cells

To assess the potential role of interleukin (IL)-7 in immunotherapy of human malignant melanoma, we have examined the lymphokine-activated killer (LAK) cell sensitivity of four human melanoma cell lines against LAK cells generated by IL-7 or IL-2. Lysis was determined by a 24-h cytotoxicity test using 3-(4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT). All melanoma cell lines were susceptible to IL-7 – and IL-2 – generated LAK cells. The sensitivity of melanoma cells to IL-2 – induced LAK cells was higher compared to IL-7 – induced LAK cells. At an effector target ratio of 20 : 1, the lysis by IL-7 – induced LAK cells ranged between 41% and 52%, whereas IL-2 – induced lysis ranged between 80% and 94% (p < 0.01). IL-7-induced LAK cells, however, showed almost no cytotoxicity towards HaCat keratinocytes and human umbilical vein endothelial cells (HUVECs). Immunophenotyping revealed a higher expression of the tac antigen (CD 25) on IL-7-generated LAK cells, particularly those cells that were CD 56 negative or CD 3 positive compared to IL-2 – induced LAK cells. In contrast, IL-2 – generated LAK cells killed 62% of the HaCat keratinocytes and 60% of the HUVECs. Secretion of tumor necrosis factor-alpha into culture supernatants was significantly higher in IL-2-generated LAK cells compared to IL-7- stimulated LAK cells (p < 0.01), whereas TNF-alpha levels of IL-7 – induced LAK cells were in the range of unstimulated lymphocytes. Because nonspecific cytotoxicity against other normal cells such as keratinocytes and endothelial cells contributes to the dose-limiting side effects of immunotherapy with IL-2, immunotherapy using IL-7 might be a better tolerated future alternative

Experimental and numerical analysis of atmospheric propagation of high energy laser

The transmission of high power laser radiation through the atmosphere is influenced by turbulent motion of the air. As a result the beam experiences an alteration regarding its position and its distribution, which increases with increasing propagation length. In order to analyze the atmospheric influence on the laser beam propagation a disk laser with a maximum output power of 6 kW and a wavelength of 1.03 µm is operated on a 130 m long free transmission laser test range in Lampoldshausen. The test range is equipped with a variety of sensors, which continuously monitor the current status of the weather conditions. Power sensors and camera systems at the beginning and the end of the test range measure the laser beam parameters before and after propagation. The experimental results are compared with a numerical analysis of the laser beam propagation performed by the software TALAP (Turbulent Atmosphere and Laser Beam Propagation), developed at the Institute of Technical Physics of DLR. It is based on the Kolmogorov turbulence model, which considers turbulent cells of different scale sizes. First measurements of power transmission, diameter of the laser beam and variations of its center of gravity are performed on a sunny and on a rainy day. The results show a good correlations to the measurements of the turbulence strength and the visibility. A comparison to the numerical analysis has shown coincidences. Future measurements will be performed at different weather conditions and seasons. Experimental results will be used to modify the simulation software, if necessary

The DNA-polymorphism rs849142 is associated with skin toxicity induced by targeted anti-EGFR therapy using cetuximab

Skin toxicity (ST) is a frequent adverse effect (AE) in anti-epidermal growth factor receptor (EGFR)-targeted treatment of metastatic colorectal cancer (mCRC) resulting in decreased quality of life and problems in clinical management. We wanted to identify biomarkers predicting ST in this setting and focused on 70 DNA polymorphisms associated with acne, the (immunoglobulin fragment crystallizable region) Fcγ-receptor pathway, and systemic lupus erythematosus (SLE) applying next-generation-sequencing (NGS). For the analysis patients with mCRC treated with cetuximab were selected from the FIRE-3 study. A training group consisting of the phenotypes low (1) - and high-grade (3) ST (n = 16) and a validation group (n = 55) representing also the intermediate grade (2) were genotyped and investigated in a genotype-phenotype association analysis. The single nucleotide polymorphism (SNP) rs849142 significantly associated with ST in both the training- (p < 0.01) and validation-group (p = 0.04). rs849142 is located in an intron of the juxtaposed with another zinc finger protein 1 (JAZF1) gene. Haplotype analysis demonstrated significant linkage disequilibrium of rs849142 with JAZF1. Thus, rs849142 might be a predictive biomarker for ST in anti-EGFR treated mCRC patients. Its value in the clinical management of AE has to be validated in larger cohorts

Targeting the undruggable: exploiting neomorphic features of fusion oncoproteins in childhood sarcomas for innovative therapies

While sarcomas account for approximately 1% of malignant tumors of adults, they are particularly more common in children and adolescents affected by cancer. In contrast to malignancies that occur in later stages of life, childhood tumors, including sarcoma, are characterized by a striking paucity of somatic mutations. However, entity-defining fusion oncogenes acting as the main oncogenic driver mutations are frequently found in pediatric bone and soft-tissue sarcomas such as Ewing sarcoma (EWSR1-FLI1), alveolar rhabdomyosarcoma (PAX3/7-FOXO1), and synovial sarcoma (SS18-SSX1/2/4). Since strong oncogene-dependency has been demonstrated in these entities, direct pharmacological targeting of these fusion oncogenes has been excessively attempted, thus far, with limited success. Despite apparent challenges, our increasing understanding of the neomorphic features of these fusion oncogenes in conjunction with rapid technological advances will likely enable the development of new strategies to therapeutically exploit these neomorphic features and to ultimately turn the \textquotedblundruggable\textquotedbl into first-line target structures. In this review, we provide a broad overview of the current literature on targeting neomorphic features of fusion oncogenes found in Ewing sarcoma, alveolar rhabdomyosarcoma, and synovial sarcoma, and give a perspective for future developments. Graphical abstract Scheme depicting the different targeting strategies of fusion oncogenes in pediatric fusion-driven sarcomas. Fusion oncogenes can be targeted on their DNA level (1), RNA level (2), protein level (3), and by targeting downstream functions and interaction partners (4)

Tribological and mechanical properties of lubricant filled microcapsules in thermoplastic composites

Polymeric materials with long lifetime and low frictional energy loss are frequently required for a broad range of applications. Microencapsulation of lubricating oils by in-situ polymerization (melamine-formaldehyde) and interfacial polymerization (polyurethane/polyurea) was used to obtain free-flowing powders, which can be used as additive for thermoplastic materials resulting in microcapsule-containing self-lubricating composites. The specific functionality of such composites is achieved via portioned and localised release of the lubricant in the areas of the interface, which experiences the highest degrees of stress and wear due to the friction. Friction-triggered on-demand release of the lubricating oil results in materials with higher wear resistance and potentially leading to new products with prolonged lifetime. In this study, different ratios of microcapsules were added in polyoxymethylene (POM) and polybutylterephthalat (PBT) matrices by using laboratory scale twin-screw extruder resulting in self-lubricating composite materials. The effect of such modification on the tribological and mechanical properties of the thermoplastic composites were investigated. Rotational ball on disc tests were used to investigate the wear loss and coefficient of friction for the composites with varied microcapsule concentrations. Tensile tests revealed decreased mechanical stability for the composites with higher microcapsule content regardless of microcapsule wall material composition. Addition of 5&nbsp;wt.-&nbsp;% of encapsulated lubricant oil led to the substantial decrease of the frictional and wear coefficients. Further increase of encapsulated lubricant oil content to 10&nbsp;wt.-% had a major decreasing impact on the mechanical properties, whilst the effect on the tribological performance was rather small

Integrative clinical transcriptome analysis reveals TMPRSS2-ERG dependency of prognostic biomarkers in prostate adenocarcinoma

In prostate adenocarcinoma (PCa), distinction between indolent and aggressive disease is challenging. Around 50% of PCa are characterized by TMPRSS2-ERG (T2E)-fusion oncoproteins defining two molecular subtypes (T2E-positive/negative). However, current prognostic tests do not differ between both molecular subtypes, which might affect outcome prediction. To investigate gene-signatures associated with metastasis in T2E-positive and T2E-negative PCa independently, we integrated tumor transcriptomes and clinicopathological data of two cohorts (total n = 783), and analyzed metastasis-associated gene- signatures regarding the T2E-status. Here, we show that the prognostic value of biomarkers in PCa critically depends on the T2E-status. Using gene-set enrichment analyses, we uncovered that metastatic T2E-positive and T2E-negative PCa arecharacterized by distinct gene-signatures. In addition, by testing genes shared by several functional gene-signatures for theirassociation with event-free survival in a validation cohort (n=272), we identifiedfive genes (ASPN,BGN,COL1A1,RRM2andTYMS)—three of which are included in commercially available prognostic tests—whose high expression was significantlyassociated with worse outcome exclusively in T2E-negative PCa. Among these genes,RRM2andTYMSwere validated byimmunohistochemistry in another validation cohort (n=135), and several of them proved to add prognostic information tocurrent clinicopathological predictors, such as Gleason score, exclusively for T2E-negative patients. No prognostic biomarkerswere identified exclusively for T2E-positive tumors. Collectively, our study discovers that the T2E-status, which ispersenot astrong prognostic biomarker, crucially determines the prognostic value of other biomarkers. Our data suggest that themolecular subtype needs to be considered when applying prognostic biomarkers for outcome prediction in PCa. What’s new? Genetic rearrangements involving androgen-regulated transmembrane protease serine 2 and genes from the ETS transcription factor family (T2E), most commonly ERG and ETV1, occur in half of prostate cancers but are currently not considered in risk predictions. The authors integrate clinical and transcriptomic data from multiple studies and show that the prognostic value of biomarkers critically depends on the T2E-status. They identify five biomarkers that predict negative outcome exclusively in T2E-negative prostate cancers, which has implications for outcome prediction based on the molecular subtype.Deutsche Forschungsgemeinschaft 391665916Deutsche Krebshilfe 70112257Dr Leopold and Carmen Ellinger FoundationDr Rolf M. Schwiete FoundationFriedrich-Baur FoundationGert and Susanna Mayer FoundationKind-Philipp FoundationMatthias-Lackas FoundationMehr LEBEN fur Krebskranke Kinder-Bettina-Brau-StiftungWilhelm Sander-Stiftung 2016.167.