Chemoresistance acquisition induces a global shift of expression of aniogenesis-associated genes and increased pro-angogenic activity in neuroblastoma cells

BACKGROUND: Chemoresistance acquisition may influence cancer cell biology. Here, bioinformatics analysis of gene expression data was used to identify chemoresistance-associated changes in neuroblastoma biology. RESULTS: Bioinformatics analysis of gene expression data revealed that expression of angiogenesis-associated genes significantly differs between chemosensitive and chemoresistant neuroblastoma cells. A subsequent systematic analysis of a panel of 14 chemosensitive and chemoresistant neuroblastoma cell lines in vitro and in animal experiments indicated a consistent shift to a more pro-angiogenic phenotype in chemoresistant neuroblastoma cells. The molecular mechanims underlying increased pro-angiogenic activity of neuroblastoma cells are individual and differ between the investigated chemoresistant cell lines. Treatment of animals carrying doxorubicin-resistant neuroblastoma xenografts with doxorubicin, a cytotoxic drug known to exert anti-angiogenic activity, resulted in decreased tumour vessel formation and growth indicating chemoresistance-associated enhanced pro-angiogenic activity to be relevant for tumour progression and to represent a potential therapeutic target. CONCLUSION: A bioinformatics approach allowed to identify a relevant chemoresistance-associated shift in neuroblastoma cell biology. The chemoresistance-associated enhanced pro-angiogenic activity observed in neuroblastoma cells is relevant for tumour progression and represents a potential therapeutic target

Development of laser-based joining technology for the fabrication of ceramic thermoelectric modules

The process of laser-induced brazing constitutes a potential option for connecting several ceramic components (n- and p-type ceramic bars and ceramic substrate) of a thermoelectric generator (TEG) unit. For the construction of the TEGs, TiOₓ and BₓC were used as thermoelectric bars and AlN was used as substrate material. The required process time for joining is well below that of conventional furnace brazing processes and, furthermore, establishes the possibility of using a uniform filler system for all contacting points within the thermoelectric unit. In the work reported here, the application-specific optimization of the laser-joining process is presented as well as the adapted design of the thermoelectric modules. The properties of the produced bonding were characterized by using fatigue strength and microstructural investigations. Furthermore, the operational reliability of the modules was verified

NOVEL IN-SITU METAL AND MINERAL EXTRACTION TECHNOLOGY

This white paper summarizes the state of art of in-situ leaching of metals and minerals, and describes a new technology concept employing improved fragmentation of ores underground in order to prepare the ore for more efficient in-situ leaching, combined with technology to continuously improve solution flow patterns through the ore during the leaching process. The process parameters and economic benefits of combining the new concept with chemical and biological leaching are described. A summary is provided of the next steps required to demonstrate the technology with the goal of enabling more widespread use of in-situ leaching

Umweltpolitik mit handelbaren Emissionsrechten : Möglichkeiten zur Verringerung der Kohlendioxid- und Stickoxidemissionen.

Emissionsrechte; Luftverunreinigung; Kohlendioxid; Stickoxid; Klimaveränderung; Deutschland; EU-Staaten;

Experimental Evaluation of Gene Silencing As New Therapeutic Option in the Treatment of Gemcitabine-chemoresistant Non-small-cell Lung Cancer

The evolution of technological and therapeutic applications of siRNA since the description of the interference process in 2006 has been extremely rapid and very productive. Currently, at least ten tumor entities and ten viral infections in which siRNA-based therapy might play an auspicious role have been described. Because of the very poor prognosis of NSCLC, we examined and proposed a new therapeutic alternative for the treatment of gemcitabine-resistant lung cancer via siRNA-specific silencing of six important molecules involved in lung carcinogenesis.Methods: One hundred thousand gemcitabine-chemoresistant A549 cell lines were cultured in a humidified atmosphere containing 5 % CO2 at 37°C and were transfected with specific siRNA targeting HIF1, HIF2, STAT3, SRF, E2F1 and Survivin. The relative expression of these molecules was examined via qRT-PCR and the viability of the chemoresistant cells after siRNA transfection was analyzed using a CASY system 72 hours after specific transfection.Results: The relative expression of the examined target molecules was suppressed by up to 73 % after specific transfection, and the CASY system demonstrated a concentration-dependent reduction in the viability of chemoresistant A549 cells of up to 61 %. Therefore the obtained results were significantly better in comparison to the control group.Conclusions: siRNA complexes may induce accurate suppression of various target molecules involved in lung tumor growth, in particular in gemcitabine- chemoresistant adenocarcinoma. Therefore, siRNA-based nanotechnology might represent a productive platform for the development of new chemotherapeutic agents for advanced stages of lung cancer in the context of a personalized multimodality regimen

A robust vegetation-based elevation transfer function for reconstructing Arctic polygon mire palaeo-microtopography

The reconstruction of past environments by means of macrofossil and pollen analysis is commonly based on the modern ecological preferences of the taxa that may have produced these fossils. Here we present a modelling approach, in which we use modern vegetation–surface height relationships to quantify past surface heights in an Arctic ice-wedge polygon mire. Vegetation composition and ground surface height (GSH) were assessed in a polygon mire near Kytalyk (Northeastern Siberia). Cluster analysis revealed five plant communities, which are clearly separated with respect to ground surface height, frost surface height and coverages of open water and vegetation. Based on the composition of modern vegetation we constructed two sets of potential fossil types (plant macrofossils and pollen), an extensive one and a more restricted one to reflect different conditions of preservation and recognisability. We applied Canonical Correspondence Analysis to model the relationships between potential fossil types and measured GSH. Both models show a strong relationship between modelled and measured GSH values and a high accuracy in prediction. Finally, we used the models to predict GSH values for Holocene peat samples and found a fair correspondence with expert-based multi-proxy reconstruction of wetness conditions, even though only a minor part of the encountered fossils were represented in the GSH models, illustrating the robustness of the approach. Our approach can be used to reconstruct palaeoenvironmental conditions in a more objective way and can serve as a template for further palaeoecological studies

Characteristics associated with quality of life among people with drug-resistant epilepsy

Quality of Life (QoL) is the preferred outcome in non-pharmacological trials, but there is little UK population evidence of QoL in epilepsy. In advance of evaluating an epilepsy self-management course we aimed to describe, among UK participants, what clinical and psycho-social characteristics are associated with QoL. We recruited 404 adults attending specialist clinics, with at least two seizures in the prior year and measured their self-reported seizure frequency, co-morbidity, psychological distress, social characteristics, including self-mastery and stigma, and epilepsy-specific QoL (QOLIE-31-P). Mean age was 42 years, 54% were female, and 75% white. Median time since diagnosis was 18 years, and 69% experienced ≥10 seizures in the prior year. Nearly half (46%) reported additional medical or psychiatric conditions, 54% reported current anxiety and 28% reported current depression symptoms at borderline or case level, with 63% reporting felt stigma. While a maximum QOLIE-31-P score is 100, participants’ mean score was 66, with a wide range (25–99). In order of large to small magnitude: depression, low self-mastery, anxiety, felt stigma, a history of medical and psychiatric comorbidity, low self-reported medication adherence, and greater seizure frequency were associated with low QOLIE-31-P scores. Despite specialist care, UK people with epilepsy and persistent seizures experience low QoL. If QoL is the main outcome in epilepsy trials, developing and evaluating ways to reduce psychological and social disadvantage are likely to be of primary importance. Educational courses may not change QoL, but be one component supporting self-management for people with long-term conditions, like epilepsy