Open Science. Research Practices in the Berlin Research Area

This report presents in detail the results of the first pilot study of the Berlin Science Survey (BSS) on the topic of open science. The term open science covers various scientific practices that aim to improve the accessibility, traceability and reusability of scientific results. The BSS specifically addressed open access publications, data sharing, code and material sharing, open peer review, and citizen science. In addition to the prevalence of the individual open science practices, attitudes and assessments of the scientists were also surveyed, providing information on the extent to which the science policy goal of expanding open science is shared among scientists

Description, Reliability and Validation of a Novel Ground-Reaction-Force-Triggered Protocol for Simulation of Tripping Perturbations During Gait

Tripping is a common cause of falls across different age populations particularly in older adults. Concerns regarding the validity of simulated-fall research protocols reside in the current literature. The purpose of this study was to develop a novel treadmill-based tripping protocol that allowed researchers to deliver unanticipated tripping perturbations during walking with a high level of timing precision. The protocol utilized a side-by-side split-belt treadmill instrumented with force platforms. Treadmill belt acceleration profiles (two levels of perturbation severity: small perturbation vs large perturbation) were delivered unilaterally when the tripped leg bore 20% of the body weight during early stance. Peak trunk flexion angle during trip recovery was the primary variable used to represent the fall recovery response and likelihood of falls. Test-retest reliability of the fall responses was examined in a group of 10 young participants; validity was examined through differentiation of the fall responses between young and older adults (age 20.9 vs. 57.1 years, n=10 per group). We found that the perturbations were precisely delivered during the early stance phase (10-45 ms after initial contact). Moreover, this protocol elicited excellent reliability of recovery responses during both perturbation severities (ICC=0.944 and 0.911). Older adults exhibited significantly greater peak trunk flexion angle than young adults (p=0.035), indicating the current protocol was valid in differentiating individuals with different levels of fall risks. This novel protocol addressed some of the issues of previous simulated-fall protocols and may be useful as a tool for future fall research and clinical intervention

»in allgemeinem Beyfall« – Giuseppe Antonio Brescianellos Instrumentalmusik am Württembergischen Hof zur Zeit Eberhard Ludwigs

»Brescianello aus Bologna, ein sehr guter und gefälliger Componist [...] Seine Kammerstücke erhielten sich viele Jahre hindurch in allgemeinem Beyfall« – So schreibt Christian Friedrich Daniel Schubart in seinen Ideen zu einer Ästhetik der Tonkunst über den Württembergischen Konzert-, Kapell- und späteren Oberkapellmeister Giuseppe Antonio Brescianello. Die wissenschaftliche Auseinandersetzung mit Brescianello ist jedoch bisher eher übersichtlich. Der Aufsatz widmet sich nun seiner Beschäftigungszeit am Württembergischen Hof in Stuttgart und Ludwigsburg (1716–1737, 1744–1751). Brescianellos Personalakte liefert dabei spannende Informationen rund um die Ernennung zum Oberkapellmeister, aber auch zum Prozedere der Entlassung aus dem Hofdienst 1737 sowie seiner erneuten Einstellung 1744. Daneben werden die zur Zeit der Regentschaft von Eberhard Ludwig entstandenen Kompositionen näher untersucht, die nachweislich für den Württembergischen Hof komponiert wurden und entsprechend einen Einblick in die Musizierpraxis vor Ort geben

'aufgeweckte Einfälle' und 'sinnreiche Gedanken' - Witz und Humor in Ouvertürensuiten Georg Philipp Telemanns

Witz und Humor können eine durchaus ernste Angelegenheit sein – insbesondere dann, wenn man die Wortbedeutung während der ersten Hälfte des 18. Jahrhunderts berücksichtigt. Denn Witz wurde damals als ein Zeichen für Bildung und als ein geistreiches Spiel angesehen. Der Humor wurde davon wiederum deutlich abgegrenzt: Zunächst einfach als Stimmung, Laune oder Charakter einer Person verstanden, rückte zunehmend das von den etablierten Normen einer Gesellschaft abweichende Verhalten in den Fokus. Diese Bedeutungsfacetten der beiden Phänomene stellen in der vorliegenden Studie Ausgangspunkte für die Betrachtung einzelner Ouvertürensuiten Georg Philipp Telemanns dar. Wie Witz und Humor in einem ambivalenten Verhältnis zu Konventionen und Normen stehen, so spielt Telemann in seinen Ouvertürensuiten vielfach mit Form- und Hörerwartungen. Programmatische Titel oder Satzüberschriften verweisen etwa auf diverse außermusikalische Gebiete und führen zu einem Spiel mit Analogien. Bei den Analysen und Interpretationen der schwerpunktmäßig herausgegriffenen Ouvertürensuiten wurden jeweils alle Einzelsätze sowie die Kompositionen als Ganzes unter Berücksichtigung ihrer (möglichen) Entstehungsumstände und dem vermutlichen Erfahrungs- und Wissenshorizont der Zeitgenossen betrachtet. Bei diesem Zusammenspiel zwischen analytischer Betrachtung und Kontextualisierung zeigt sich, in welch durchdachter und vielfältiger musikalischer Gestaltung Telemann die diversen Ereignisse und Strömungen seiner Zeit auch auf Seiten der Ouvertürensuiten rezipierte und musikalisch verarbeitete. Außerdem wird deutlich, dass das damalige Verständnis von Witz und Humor als ein Spiel mit Konventionen und dem Darstellen von Charakteren auf dem Gebiet der Instrumentalmusik ebenfalls eine wichtige Rolle spielt

Characterization of cell spheroids as promising tool as 3D printable building blocks for vascular network formation

IntroductionThe human vasculature is a highly structured and organized system to supply each cell in the body with oxygen and nutrients and remove metabolic waste. Blood vessels mainly consist of three different cell types. The inner layer (Tunica Intima) of endothelial cells which form a monolayer which are responsible for new blood vessel formation, allow blood flow and also act as a semi-selective barrier to the surrounding tissue followed by the middle layers (Tunica media) of mural cells (smooth muscle cells and pericytes) which are responsible for the vessel maturation and stabilisation. The outer layer (Tunica adventitia) consists mostly of fibrous connective tissue and myofibroblast which can act as progenitor cells. One promising tool to recreate a vascular network in artificial tissue constructs is the use of 3D printable spheroids. 3D printing in general offers the opportunity to have spatial control about release of different materials depending on its properties. In this project we are aiming for using cell spheroids as a 3D printable material. Spheroids display a scaffold free multicellular tissue construct which is characterized by three dimensional cellular self-assembly and by strong cell-cell and cell-ECM interactions1. Furthermore spheroids represent more physiological and functional characteristics compared to 2D cell culture 3,4. By using spheroids consisting of cells which reflect the physiological cell composition and having the ability to fuse with each other to larger scale multicellular constructs, they show a promising potential for usage as printable building blocks AimCultivation and characterisation of cell spheroids consisting of different cell types regarding their time related compaction rate and fusion ability as prediction for use as 3D printable building blocks. Additional analysis of cell survival and cell proliferation at different states of the spheroid characterization.Materials and MethodsWe use manufactured SU8/Si wafer as a positive mold to create patterned elastomeric stamps of poly (dimethylsiloxane) (PDMS) for microwell array platforms. A 4 % agarose solution was cast onto the PDMS stamp for non-adherent cell spheroid culture to cultivate spheroids made of 100 % smooth muscle cells (SMC), 100 % mesenchymal stem cells (MSC) and a co-culture of 90 % SMC and 10 % human umbilical vein endothelial cells (HUVEC). Cell spheroids, consisting each of approximately 267 cells, were cultivated for 9 days to analyse the spheroid formation and spheroid compaction over time using a custom developed MATLAB based program for automate data analysis. Spheroids at day 9 were stained for Live/Dead and Ki67. Afterwards ,the spheroids were transferred to another agarose made microwell array platform to analyse the fusion between different spheroids of the same cell types (MSC-Spheroid : MSC-Spheroid, SMC-Spheroid : SMC-Spheroid, SMC-HUVEC-Spheroid : SMC-HUVEC-Spheroid) and spheroids of different cell types (SMC-Spheroid : MSC-Spheroid, SMC-HUVEC-Spheroid : MSC-Spheroid) for 48 hours by using different cell trackers with subsequent staining for Live/Dead and Ki67. Figure 1. Schematic overview of the current workflow to analyse spheroid cultivation, compaction and fusion as a final use as 3D printable building blocks Results and ConclusionsDepending on the cellular composition of the spheroids, different compaction times could be observed, resulting in a final size range of 70-120µm despite the same cell number in each spheroid type. After the final compaction it could be shown, that the spheroids didn’t developed a necrotic core or specific proliferation zones. Due to the differences in final compaction size, heterologous spheroid fusion showed a different dynamic compared to homolog spheroid fusion.References1. Whitesides GM, Grzybowski B. Self-assembly at all scales. Science 2002; 295: 2418–2132. Fukuda J, Nakazawa K. Orderly Arrangement of Hepatocyte Spheroids on a Microfabricated Chip. Tissue Eng 2005; 11: 1254–1262.3. Bhang SH, Cho S-W, La W-G, Lee T-J, Yang HS, Sun A-Y et al. Angiogenesis in ischemic tissue produced by spheroid grafting of human adipose-derived stromal cells. Biomaterials 2011; 32: 2734–2747.AcknowledgementsThis work is supported by an ERC Consolidator Grant under grant agreement no 724469.<br/

Renal Transporter-Mediated Drug-Biomarker Interactions of the Endogenous Substrates Creatinine and N1 -Methylnicotinamide : A PBPK Modeling Approach

Endogenous biomarkers for transporter-mediated drug-drug interaction (DDI) predictions represent a promising approach to facilitate and improve conventional DDI investigations in clinical studies. This approach requires high sensitivity and specificity of biomarkers for the targets of interest (e.g., transport proteins), as well as rigorous characterization of their kinetics, which can be accomplished utilizing physiologically-based pharmacokinetic (PBPK) modeling. Therefore, the objective of this study was to develop PBPK models of the endogenous organic cation transporter (OCT)2 and multidrug and toxin extrusion protein (MATE)1 substrates creatinine and N1-methylnicotinamide (NMN). Additionally, this study aimed to predict kinetic changes of the biomarkers during administration of the OCT2 and MATE1 perpetrator drugs trimethoprim, pyrimethamine, and cimetidine. Whole-body PBPK models of creatinine and NMN were developed utilizing studies investigating creatinine or NMN exogenous administration and endogenous synthesis. The newly developed models accurately describe and predict observed plasma concentration-time profiles and urinary excretion of both biomarkers. Subsequently, models were coupled to the previously built and evaluated perpetrator models of trimethoprim, pyrimethamine, and cimetidine for interaction predictions. Increased creatinine plasma concentrations and decreased urinary excretion during the drug-biomarker interactions with trimethoprim, pyrimethamine, and cimetidine were well-described. An additional inhibition of NMN synthesis by trimethoprim and pyrimethamine was hypothesized, improving NMN plasma and urine interaction predictions. To summarize, whole-body PBPK models of creatinine and NMN were built and evaluated to better assess creatinine and NMN kinetics while uncovering knowledge gaps for future research. The models can support investigations of renal transporter-mediated DDIs during drug development

Predicting the Effect of Indirect Cell Kill in the Treatment of Multiple Brain Metastases via Single-Isocenter/Multitarget Volumetric Modulated Arc Therapy Stereotactic Radiosurgery

PURPOSE: Due to spatial uncertainty, patient setup errors are of major concern for radiosurgery of multiple brain metastases (m-bm) when using single-isocenter/multitarget (SIMT) volumetric modulated arc therapy (VMAT) techniques. However, recent clinical outcome studies show high rates of tumor local control for SIMT-VMAT. In addition to direct cell kill (DCK), another possible explanation includes the effects of indirect cell kill (ICK) via devascularization for a single dose of 15 Gy or more and by inducing a radiation immune intratumor response. This study quantifies the role of indirect cell death in dosimetric errors as a function of spatial patient setup uncertainty for stereotactic treatments of multiple lesions. MATERIAL AND METHODS: Nine complex patients with 61 total tumors (2-16 tumors/patient) were planned using SIMT-VMAT with geometry similar to HyperArc with a 10MV-FFF beam (2400 MU/min). Isocenter was placed at the geometric center of all tumors. Average gross tumor volume (GTV) and planning target volume (PTV) were 1.1 cc (0.02–11.5) and 1.9 cc (0.11–18.8) with an average distance to isocenter of 5.4 cm (2.2–8.9). The prescription was 20 Gy to each PTV. Plans were recalculated with induced clinically observable patient setup errors [±2 mm, ±2o] in all six directions. Boolean structures were generated to calculate the effect of DCK via 20 Gy isodose volume (IDV) and ICK via 15 Gy IDV minus the 20 Gy IDV. Contributions of each IDV to the PTV coverage were analyzed along with normal brain toxicity due to the patient setup uncertainty. Induced uncertainty and minimum dose covering the entire PTV were analyzed to determine the maximum tolerable patient setup errors to utilize the ICK effect for radiosurgery of m-bm via SIMT-VMAT. RESULTS: Patient setup errors of 1.3 mm /1.3° in all six directions must be maintained to achieve PTV coverage of the 15 Gy IDV for ICK. Setup errors of ±2 mm/2° showed clinically unacceptable loss of PTV coverage of 29.4 ± 14.6% even accounting the ICK effect. However, no clinically significant effect on normal brain dosimetry was observed. CONCLUSIONS: Radiosurgery of m-bm using SIMT-VMAT treatments have shown positive clinical outcomes even with small residual patient setup errors. These clinical outcomes, while largely due to DCK, may also potentially be due to the ICK. Potential mechanisms, such as devascularization and/or radiation-induced intratumor immune enhancement, should be explored to provide a better understanding of the radiobiological response of stereotactic radiosurgery of m-bm using a SIMT-VMAT plan

Open Science. Forschungspraktiken im Berliner Forschungsraum

In diesem Report werden die Ergebnisse der ersten Pilotstudie des Berlin Science Survey (BSS) zum Themenblock Open Science detailliert vorgestellt. Unter dem Begriff Open Science werden verschiedene wissenschaftliche Praktiken zusammengefasst, die die Verbesserung der Zugänglichkeit, Nachvollziehbarkeit und Nachnutzbarkeit von wissenschaftlichen Ergebnissen zum Ziel haben. Im BSS wurden Open Access Publikationen, Data Sharing, Code und Material Sharing, Open Peer Review und Citizen Science thematisiert. Neben der Verbreitung der einzelnen Open Science Praktiken wurden auch Einstellungen und Einschätzungen der Wissenschaftler:innen erhoben, die Aufschluss darüber geben, inwiefern das wissenschaftspolitische Ziel einer Ausweitung von Open Science geteilt wird

AMEAÇAS E DESASTRES NATURAIS NA AMAZÔNIA SUL OCIDENTAL: ANÁLISE DA BACIA DO RIO PURUS

A região Sul Ocidental da Amazônia no Brasil registra numerosos eventos hidroclimáticos extremos e desastres naturais, mas poucos trabalhos as analisam na escala de bacias hidrográficas. Com vistas a contribuir para a gestão de risco de desastres na Amazônia, esta pesquisa analisa as ameaças e os desastres naturais na bacia transfronteiriça do rio Purus. São empregados dados fluviométricos, documentos oficiais de organismos de defesa civil e informações de artigos jornalísticos para identificação, descrição e mapeamento das ameaças e desastres entre 1971 e 2012. Foram identificados 17 anos com variações hidrológicas extremas, 104 registros de desastres associados ao incremento e à intensa redução das precipitações com mais de 400.000 pessoas afetadas e danos materiais, ambientais, sociais e econômicos acima 450 milhões de Reais. As áreas mais ameaçadas são os municípios de Rio Branco (AC) e Boca do Acre (AM), situadas na região do alto curso da bacia do rio Purus, e que registram as maiores populações da bacia. Concluiu-se que uma abordagem holística dos fatores e processos envolvidos numa unidade de analise como a bacia hidrográfica e a quantificação de danos e prejuízos são elementos fundamentais no subsidio as discussões acerca do planejamento e gestão de riscos de desastres na Amazônia