Practitioner’s Section: Integrated Resource Efficiency Analysis for Reducing Climate Impacts in the Chemical Industry

Reducing greenhouse gas emissions of the material-intensive chemical industry requires an integrated analysis and optimization of the complex production systems including raw material and energy use, resulting costs and environmental and climate impacts. To meet this challenge, the research project InReff (Integrated Resource Efficiency Analysis for Reducing Climate Impacts in the Chemical Industry) has been established. It aims at the development of an IT-supported modeling and evaluation framework which is able to comprehensively address issues of resource efficiency and climate change within the chemical industry, e.g. the minimization of material and energy intensity and consequently greenhouse gas emissions, without compromising on production performance. The paper presents background information on resource efficiency and the research project, an ideal-typical decision model for resource efficiency analysis, the conceptual approach for an IT-based integration platform as well as the case study design at the industrial project partners’ sites. These first results are linked to future activities and further research questions are highlighted in the concluding section

Glioneuronal tumor with ATRX alteration, kinase fusion and anaplastic features (GTAKA): a molecularly distinct brain tumor type with recurrent NTRK gene fusions

Glioneuronal tumors are a heterogenous group of CNS neoplasms that can be challenging to accurately diagnose. Molecular methods are highly useful in classifying these tumors-distinguishing precise classes from their histological mimics and identifying previously unrecognized types of tumors. Using an unsupervised visualization approach of DNA methylation data, we identified a novel group of tumors (n = 20) that formed a cluster separate from all established CNS tumor types. Molecular analyses revealed ATRX alterations (in 16/16 cases by DNA sequencing and/or immunohistochemistry) as well as potentially targetable gene fusions involving receptor tyrosine-kinases (RTK; mostly NTRK1-3) in all of these tumors (16/16; 100%). In addition, copy number profiling showed homozygous deletions of CDKN2A/B in 55% of cases. Histological and immunohistochemical investigations revealed glioneuronal tumors with isomorphic, round and often condensed nuclei, perinuclear clearing, high mitotic activity and microvascular proliferation. Tumors were mainly located supratentorially (84%) and occurred in patients with a median age of 19 years. Survival data were limited (n = 18) but point towards a more aggressive biology as compared to other glioneuronal tumors (median progression-free survival 12.5 months). Given their molecular characteristics in addition to anaplastic features, we suggest the term glioneuronal tumor with ATRX alteration, kinase fusion and anaplastic features (GTAKA) to describe these tumors. In summary, our findings highlight a novel type of glioneuronal tumor driven by different RTK fusions accompanied by recurrent alterations in ATRX and homozygous deletions of CDKN2A/B. Targeted approaches such as NTRK inhibition might represent a therapeutic option for patients suffering from these tumors

Local control of protein binding and cell adhesion by patterned organic thin films

Control of the cell adhesion and growth on chemically patterned surfaces is important in an increasing number of applications in biotechnology and medicine, for example implants, in-vitro cellular assays, and biochips. This review covers patterning techniques for organic thin films suitable for site-directed guidance of cell adhesion to surfaces. Available surface patterning techniques are critically evaluated, with special emphasis on surface chemistry that can be switched in time and space during cultivation of cells. Examples from the authors' laboratory include the use of cell-repellent self-assembled monolayers (SAM) terminated by oligoethylene glycol (OEG) units and the lifting of the cell repellent properties by use of electrogenerated Br2/HOBr which can be performed with positionable microelectrodes. Structural changes of the SAM were analyzed by polarization-modulated infrared reflection absorption spectroscopy (PM IRRAS). Use of a soft array system of individually addressable microelectrodes enables formation of flexible and complex patterns in a short time and has the potential for further acceleration of probe-induced local manipulation of cell adhesion

The promoter of human telomerase reverse transcriptase is activated during liver regeneration and hepatocyte proliferation.

Telomerase activity has not been detected in healthy human liver biopsy samples, but it is up-regulated in most human liver tumors. It is not clear whether telomerase is activated in response to acute or chronic liver injury. Telomerase activity is closely associated with expression of its catalytic subunit, telomerase reverse transcriptase (TERT). We analyzed the activity of the human TERT (hTERT) promoter during liver regeneration in vivo and hepatocyte proliferation in vitro

14 Years of PID Services at the German National Library of Science and Technology (TIB): Connected Frameworks, Research Data and Lessons Learned from a National Research Library Perspective

In an ideal research world, any scientific content should be citable and the coherent content, as well as the citation itself, should be persistent. However, today’s scientists do not only produce traditional research papers – they produce comprehensive digital resources and collections. TIB’s mission is to develop a supportive framework for a sustainable access to such digital content – focusing on areas of engineering as well as architecture, chemistry, information technology, mathematics and physics. The term digital content comprises all digitally available resources such as audiovisual media, databases, texts, images, spreadsheets, digital lab journals, multimedia, 3D objects, statistics and software code. In executing this mission, TIB provides services for the management of digital content during ongoing and for finished research. This includes:   - a technical and administrative infrastructure for indexing, cataloguing, DOI registration and licensing for text and digital objects, namely the TIB DOI registration which is active since 2005,   - the administration of the ORCID DE consortium, an institutional network fostering the adoption of ORCID across academic institutions in Germany,   - training and consultancy for data management, complemented with a digital repository for the deposition and provision of accessible, traceable and citable research data (RADAR),   - a Research and Development Department where innovative projects focus on the visualization and the sustainable access to digital information, and   - the development of a supportive framework within the German research data community which accompanies the life cycle of scientific knowledge generation and transfer. Its goal is to harmonize (meta)data display and exchange primarily on a national level (LEIBNIZ DATA project)

Studies on the impact of probiotic bacteria on enteric microbial diversity and immune response

The mechanism of action of probiotics is based on competitive exclusion and immune modulation. However, the literature is scant on supporting data because of the failure to adopt a systems approach to probiotic functionality. This has been partially addressed in this thesis by taking into consideration the tripartite interaction between bacteria and bacteria in the enteric community; between bacteria and the host animal and finally, between the host immune response (innate or acquired) on the plethora of microbes that inhabit the gastrointestinal tract. A trial involving newly inducted cattle in a feedlot, formed the basis of initial attempts to assess the benefits of a commercial probiotic formulation - Protexin on intestinal health by enumeration of a select subset of cultivable bacteria species and by assessment of immune modulation. The results failed to demonstrate a significant change in the population dynamics of cultured faecal microbes but did show that Protexin stimulated immune responsiveness in T cells. Carcass analysis demonstrated a significant reduction in marbling or intramuscular fat deposition. In the course of examining the faecal microflora from feedlot cattle, the presence of high levels of Bacillus spores suggested that one possible reason for the lack of a growth benefit may be attributed to a high endogenous level of bacilli. Since there were no reliable methodologies for identifying Bacillus species, an alternative procedure was developed involving amplified ribosomal DNA restriction analysis (ARDRA). With this protocol, we were able to show that cattle faeces contained large numbers of Bacillus spores representing different mesophilic species, where B. subtilis, B. licheniformis and B. clausii dominated. The presence of a stable population of coliforms in cattle faeces that was not altered by probiotic feeding highlighted the importance of developing better techniques to characterise diversity in E. coli, a potential food-borne pathogen of economic significance to the cattle industry. The use of virulence genes to genotype coliforms provided a method for differentiating between pathogenic, clinical and commensal isolates of E. coli. Altogether, a combination of uni- and multiplex PCR assays was developed to screen for 50 virulence genes (VGs) from 8 pathotypes of E. coli. There was a significant association between phylogroupings and VG ownership. This result showed clearly that the lack of or possession of VGs in member isolates of each phylogenetic group can be used to assess diversity and potential pathogenesis of E. coli. To understand better the importance of pathogenic enteric coliforms, an alternative animal model involving pigs with post-weaning diarrhoea was used to investigate the relationship between pathogenicity and commensalism by VG profiling. Porcine enterotoxigenic E. coli (ETEC) were found to carry VGs identified in E. coli that cause extraintestinal infection. Furthermore, by using the appropriate methods of statistical analysis, VG profiling had the capacity to predict the pathogenic and commensal status of individual clones. By developing the capacity to rapidly characterise and genotype virulence and commensalism in E. coli, it is now feasible to examine how probiotic feeding can modulate the population dynamics of different community members in pigs with enteric disease, as well as changes in the coliform populations. Finally, another arm of the tripartite interaction involving bacteria and host interaction was modelled in vitro by examining the primary signalling events between bacteria and intestinal epithelial cells. These investigations focused on the judicious selection of T84 as the reporter intestinal epithelial cell line because of low level expression of inflammatory transcripts from 6 other epithelial cell lines. Using a panel of coliforms genotyped for virulence or lack of virulence, the signalling events that followed on from the primary interaction between bacterium and cell, showed there was a lack of correlation between VGs and gene activation. Nonetheless, all the coliform strains tested varied in their capacity to signal transduce T84, confirming that this differential bioactivity can be exploited in the ranking of candidate probiotic strains. The differential responses seen with different E. coli strains and the lower and more consistent activation patterns recorded by LABs for both cytokine and chemokine gene activation, demonstrate that a semi-quantitative ranking of microbial bioactivity can be obtained. Such an approach if adopted in conjunction with an even wider panel of genes in a standardised in vitro environment can provide invaluable information on the selection of appropriate strains to be further tested in vivo

An annotated checklist of macrozoobenthic species in German waters of the North and Baltic Seas

Abstract The present compilation is the first attempt to generate a comprehensive list of all macrozoobenthic species recorded at least once in the German regions of the North Sea and Baltic Sea including non-indigenous species and freshwater species which occurred in brackish waters (estuaries, bays, fjords etc.). Based on the data of several research institutes and consultancies, the macrozoobenthic species inventory comprises a total of 1.866 species belonging to 16 phyla including 193 threatened species. The most common groups were: malacostracan crustaceans (21%), Polychaeta (19%), and Gastropoda (12%). Even though the two major marine regions are separated by only 50 km of land, the composition of the respective communities was different. The two seas shared only 36.6% of the recorded species which should have profound and far-reaching consequences for conservation purposes. Considering all macroinvertebrates listed 96 species, or the equivalent of 5.2%, were introduced mainly during the last two centuries. Both seas are heavily affected by human activities and are sensitive to climate change displayed by effects on the faunal compositions. The present checklist is an important step to document these changes scientifically and may act as a base for political and management decisions

Treatment plan comparison of proton vs photon radiotherapy for lower-grade gliomas

Background and purpose: Patients with lower-grade gliomas are long-term survivors after radiotherapy and may benefit from the reduced dose to normal tissue achievable with proton therapy. Here, we aimed to quantify differences in dose to the uninvolved brain and contralateral hippocampus and compare the risk of radiation-induced secondary cancer for photon and proton plans for lower-grade glioma patients. Materials and methods: Twenty-three patients were included in this in-silico planning comparative study and had photon and proton plans calculated (50.4 Gy(RBE = 1.1), 28 Fx) applying similar dose constraints to the target and organs at risk. Automatically calculated photon plans were generated with a 3 mm margin from clinical target volume (CTV) to planning target volume. Manual proton plans were generated using robust optimisation on the CTV. Dose metrics of organs at risk were compared using population mean dose-volume histograms and Wilcoxon signed-rank test. Secondary cancer risk per 10,000 persons per year (PPY) was estimated using dose-volume data and a risk model for secondary cancer induction. Results: CTV coverage (V95%>98%) was similar for the two treatment modalities. Mean dose (D-mean) to the uninvolved brain was significantly reduced from 21.5 Gy (median, IQR 17.1-24.4 Gy) with photons compared to 10.3 Gy(RBE) (8.1-13.9 Gy(RBE)) with protons. D-mean to the contralateral hippocampus was significantly reduced from 6.5 Gy (5.4-11.7 Gy) with photons to 1.5 Gy(RBE) (0.4-6.8 Gy(RBE)) with protons. The estimated secondary cancer risk was reduced from 6.7 PPY (median, range 3.3-10.4 PPY) with photons to 3.0 PPY (1.3-7.5 PPY) with protons. Conclusion: A significant reduction in mean dose to uninvolved brain and contralateral hippocampus was found with proton planning. The estimated secondary cancer risk was reduced with proton therapy