Identifying the druggable interactome of EWS-FLI1 reveals MCL-1 dependent differential sensitivities of Ewing sarcoma cells to apoptosis inducers

Ewing sarcoma (EwS) is an aggressive pediatric bone cancer in need of more effective therapies than currently available. Most research into novel targeted therapeutic approaches is focused on the fusion oncogene EWSR1-FLI1, which is the genetic hallmark of this disease. In this study, a broad range of 3,325 experimental compounds, among them FDA approved drugs and natural products, were screened for their effect on EwS cell viability depending on EWS-FLI1 expression. In a network-based approach we integrated the results from drug perturbation screens and RNA sequencing, comparing EWS-FLI1-high (normal expression) with EWS-FLI1-low (knockdown) conditions, revealing novel interactions between compounds and EWS-FLI1 associated biological processes. The top candidate list of druggable EWS-FLI1 targets included genes involved in translation, histone modification, microtubule structure, topoisomerase activity as well as apoptosis regulation. We confirmed our in silico results using viability and apoptosis assays, underlining the applicability of our integrative and systemic approach. We identified differential sensitivities of Ewing sarcoma cells to BCL-2 family inhibitors dependent on the EWS-FLI1 regulome including altered MCL-1 expression and subcellular localization. This study facilitates the selection of effective targeted approaches for future combinatorial therapies of patients suffering from Ewing sarcoma.(VLID)471264

Hygienekontrolle von Betriebs- und Spülwasser in Kellereien mittels Kikkoman Lumitester PD-20 und ATP-Teststäbchen

In this experiment RLU (relative light units) values of water of the filling stations of six wineries were examined before and after cleaning. For measurements of the ATP amounts an instrument from Kikkoman was used. This technique is very well suited for cleaning inspection. It shows quickly if the surface of filling station or water is clean or dirty. In this experiment rinse water of six wineries has been tested with LuciPac Pen (cotton swab for surface inspection) and LuciPac Pen-Aqua (special pens for water analysis). For most of the samples, the ATP measurements were made immediately after sample collection, with the remaining samples, the RLU values were taken only in the laboratory. The average ATP values of tap waters are approximately 20 RLU in Austria. This value agrees well with the water value of the Education and Research Center of Viticulture and Pomology in Klosterneuburg. The RLU amount was around 15 RLU. In wineries where well water was used as process water, dangerous germs were isolated. These bacteria were identified by Vitek 2 compact as soil bacteria of the family Pseudomonaceae

Predição da Temperatura do Ferro-Gusa em um Alto-Forno utilizando Redes Neurais LSTM

Due to the importance of the steel industry in the national economy and the inherent complexity of operating a blast furnace, it is necessary to study ways to optimize its operation and the consumption of resources, therefore, this work aims to investigate the use of the LSTM (Long Short Term Memory) neural network to perform the prediction of the next temperature of the hot metal being produced. In this way, it is possible to support the work of the blast furnace operators, in order to optimize the consumption of resources to keep the blast furnace operating. With the results obtained from the experiments using the blast furnace operating data as a time series, it is concluded that the use of LSTM is satisfactory and that improvement of these experiments will meet the needs of the steel industry. The best result for LSTM, using 2 layers and 2048 neurons, achieved a Root Mean Square Error of 11.82ºC

Conversão Semi-automática de Algoritmos Sequenciais de Processamento Digital de Imagens para Algoritmos Paralelos na Arquitetura CUDA

Sistemas de processamento digital de imagens podem ter tempo de execução não compatíveis com o esperado pelo usuário. Uma possível solução é o uso de processamento paralelo para diminuir o tempo de execução de algoritmos de processamento de imagens. A tecnologia CUDA oferece uma interface de desenvolvimento para tirar proveito do processamento paralelo em GPUs, entretanto, possui uma alta curva de aprendizagem e exige conhecimento de recursos específicos, como sua arquitetura e tipos de memória. Este trabalho propõe uma ferramenta semi-automática para converter algoritmos de processamento de imagens sequenciais em uma versão paralela para GPU na qual o programador não precisa conhecer os detalhes da arquitetura, nem os seus comandos de programação específicos. Para tanto, o programador deve adotar a definição da API deste trabalho, seguindo os protótipos de funções e incluir, em seu código fonte, diretivas que identifiquem uma das quatro categorias de processamento: operações pixel a pixel, operações de vizinhança de pixel, operações que reduzem a imagem para um valor escalar e operações que reduzem a imagem para um vetor. O resultado final é o código fonte paralelizado na tecnologia CUDA. Foram realizados experimentos para cada uma das categorias e os resultados mostraram que a versão paralela diminui o tempo de execução para três categorias, exceto a de operações que reduzem a imagem para um vetor devido aos acessos simultâneos ao mesmo endereço de memória da posição do vetor

Long-term Administration of Pancuronium and Pipecuronium in the Intensive Care Unit

This study was performed to determine the optimum dose of pancuronium (n = 30) and pipecuronium (n = 30) under continuous sedation and analgesia in the intensive care unit (ICU). This was an open clinical investigation in 60 critically ill patients with head injury, multiple trauma (in some complicated with sepsis and multi-organ failure), requiring neuromuscular block for ventilation for at least 48 h. Emphasis was placed on the neuromuscular monitoring with a peripheral nerve stimulator and adequate sedation and analgesia. Satisfactory block was achieved in all cases with an average dose of 3 mg/h with either compound. None of the patients experienced prolonged paralysis, muscle weakness, or other neuromuscular dysfunctions in the postventilatory period. We suggest that adequate use of sedative hypnotics and opioids plus neuromuscular monitoring allowed us to optimize the dose of muscle relaxants according to the need of individual patients.</p

Wissen zum Schweizer Hochschul- und Wissenschaftsraum - Positionspapier REHES

Zur Relevanz von Forschung zu Hochschulen und Wissenschaft: Die Bedeutung von Hochschulen und der von ihnen erfüllten gesellschaftlichen Leistungen in Forschung und Bildung hat in den letzten Jahrzehnten nochmals erheblich zugenommen. Der gesellschaftliche «Nutzen» von Hochschulen spielt eine zunehmend wichtigere Rolle und die Interaktionen zwischen gesellschaftlichen Akteuren und Hochschulen nehmen zu. Diese Entwicklungen führen zu einem quantitativen und qualitativen Wachstum sowie zu internen Wandlungsprozessen in Hochschulorganisationen und dem Wissenschaftssystem. Im Rahmen solcher tiefgreifenden Veränderungen gewinnt wissenschaftlich fundiertes Wissen über Strukturen, Akteure und Prozesse in Hochschulen und Wissenschaft stark an Relevanz. Besonders für Hochschulen selbst aber auch für Stakeholder in ihrer Umwelt, leistet robustes Wissen über komplexe Sachverhalte und Entwicklungen in Hochschulen und der Wissenschaft eine wichtige Orientierungsfunktion und bietet wesentliche Entscheidungsgrundlagen. Im Ausland hat dies zur Ausdifferenzierung eines interdisziplinären Forschungszweigs geführt. Insofern erstaunt es, dass die Schweiz durch eine sehr geringe Institutionalisierung dieses Forschungszweigs charakterisiert ist. Stärkere Institutionalisierung des Austauschs von Forschenden: Das Ziel der Initiative «Research on Higher Education and Science in Switzerland» (REHES) besteht deshalb darin, Wissenschaftlerinnen und Wissenschaftler, die sich aus unterschiedlichen disziplinären Perspektiven mit Hochschulen und Wissenschaft befassen, stärker miteinander zu vernetzen und in einen stärkeren Austausch zu bringen. Ausserdem sollen auch relevante Stakeholder in diesen Austausch einbezogen werden, um einerseits Einsichten der Forschung in relevante Handlungsfelder wie Hochschulmanagement oder Forschungspolitik zu vermitteln, andererseits aber auch, um Fragen aus diesen Feldern in die Forschung einzuspeisen. Thematische Forschungslinien und Institutionalisierungsformen: Um den Austausch der Forschung zu Hochschulen und Wissenschaft in der Schweiz stärker zu institutionalisieren, braucht es zum einen konsensfähige thematische Forschungslinien, an denen sich zukünftige Forschung orientieren kann, und die international anschlussfähig ist. Es wird vorgeschlagen, den Fokus auf vier verschiedene Ebenen zu legen und diese auch in ihrem Wechselspiel zu untersuchen: Wissensgesellschaft, Hochschulsystem, Hochschulorganisation und Hochschulangehörige. Auf allen Ebenen sollen Strukturen und Prozesse sowie deren Voraussetzungen und Outcomes untersucht werden. Zum anderen bedarf es Vorschläge, wie der Austausch vor allem innerhalb der wissenschaftlichen Community organisiert werden kann. Um die Adressierbarkeit der wissenschaftlichen Gemeinschaft für Stakeholder zu erleichtern und auch handlungsrelevantes Wissen verfügbar zu machen, bedarf es einer Schnittstelle zwischen diesen beiden Akteursgruppen. Drei Varianten, die diese Zielsetzungen erfolgen, werden im Papier ausgeführt: Netzwerk REHES, Fachgesellschaft REHES und Arbeitskreis REHES in bestehender Fachgesellschaft. Sowohl die thematischen Forschungslinien als auch die Institutionalisierungsformen basieren auf Diskussionen mit Wissenschaftlerinnen und Wissenschaftlern, die sich mit diesem Forschungsfeld befassen, als auch mit Stakeholdern der Schweizer Hochschul- und Wissenschaftslandschaft