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During the design phase of a chemical plant, information is created by various software tools and stored in heterogeneous formats, such as technical documents, CAE databases, or simulation files. Eventually, these scattered information items need to be merged and consolidated. However, there is no efficient computer support for this task available today. While existing technologies like XML are capable of handling the structural and syntactic differences between the heterogeneous formats, these technologies cannot resolve any semantic incompatibilities. For this reason, information integration is still largely performed manually – a task which is both tedious and error-prone. Semantic technologies based on ontologies have been identified as an appropriate means to establish semantic interoperability. This contribution presents an ontology-based approach for information integration in chemical process engineering. The underlying knowledge base, which is based on the formal ontology OntoCAPE, is presented, and the design and implementation of a prototypical integration software are described. Further, the application of the software prototype in a large industrial use case is reported.

Alzheimer's disease (AD) is characterized by amyloid-beta (Aβ)-containing plaques, neurofibrillary tangles, and neuron and synapse loss. Tangle formation has been reproduced in P301L tau transgenic pR5 mice, whereas APP sw PS2 N141I double-transgenic APP152 mice develop Aβ plaques. Cross-breeding generates triple transgenic ( triple AD) mice that combine both pathologies in one model. To determine functional consequences of the combined Aβ and tau pathologies, we performed a proteomic analysis followed by functional validation. Specifically, we obtained vesicular preparations from triple AD mice, the parental strains, and nontransgenic mice, followed by the quantitative mass-tag labeling proteomic technique iTRAQ and mass spectrometry. Within 1,275 quantified proteins, we found a massive deregulation of 24 proteins, of which one-third were mitochondrial proteins mainly related to complexes I and IV of the oxidative phosphorylation system (OXPHOS). Notably, deregulation of complex I was tau dependent, whereas deregulation of complex IV was Aβ dependent, both at the protein and activity levels. Synergistic effects of Aβ and tau were evident in 8-month-old triple AD mice as only they showed a reduction of the mitochondrial membrane potential at this early age. At the age of 12 months, the strongest defects on OXPHOS, synthesis of ATP, and reactive oxygen species were exhibited in the triple AD mice, again emphasizing synergistic, age-associated effects of Aβ and tau in perishing mitochondria. Our study establishes a molecular link between Aβ and tau protein in AD pathology in vivo, illustrating the potential of quantitative proteomics.

Die Goeken backen GmbH ist ein Traditionsunternehmen mit Grundung im Jahr 1898. Das mittlerweile in der funften Generation betriebene Unternehmen mit Hauptsitz in Bad Driburg beschaftigt derzeit ca. 540 Mitarbeiter und verkauft die Produkte in 52 Backereifachgeschaften im gesamten Umkreis um Paderborn.

Nicotine, a component of tobacco, is highly addictive but possesses beneficial properties such as cognitive improvements and memory maintenance. Involved in these processes is the neuronal nicotinic acetylcholine receptor (nAChR) α7, whose activation triggers depolarization, intracellular signaling cascades, and synaptic plasticity underlying addiction and cognition. It is therefore important to investigate intracellular mechanisms by which a cell regulates α7 nAChR activity. We have examined the role of phosphorylation by combining molecular biology, biochemistry, and electrophysiology in SH-SY5Y neuroblastoma cells,Xenopusoocytes, rat hippocampal interneurons, and neurons from the supraoptic nucleus, and we found tyrosine phosphorylation of α7 nAChRs. Tyrosine kinase inhibition by genistein decreased α7 nAChR phosphorylation but strongly increased acetylcholine-evoked currents, whereas tyrosine phosphatase inhibition by pervanadate produced opposite effects. Src-family kinases (SFKs) directly interacted with the cytoplasmic loop of α7 nAChRs and phosphorylated the receptors at the plasma membrane. SFK inhibition by PP2 [4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine] or SU6656 (2,3-dihydro-N,N-dimethyl-2-oxo-3-[(4,5,6,7-tetrahydro-1H-indol-2-yl)methylene]-1H-indole-5-sulfonamide) increased α7 nAChR-mediated responses, whereas expression of active Src reduced α7 nAChR activity. Mutant α7 nAChRs lacking cytoplasmic loop tyrosine residues because of alanine replacement of Tyr-386 and Tyr-442 were more active than wild-type receptors and insensitive to kinase or phosphatase inhibition. Because the amount of surface α7 receptors was not affected by kinase or phosphatase inhibitors, these data show that functional properties of α7 nAChRs depend on the tyrosine phosphorylation status of the receptor and are the result of a balance between SFKs and tyrosine phosphatases. These findings reveal novel regulatory mechanisms that may help to understand nicotinic receptor-dependent plasticity, addiction, and pathology.

Biomarkers are needed to elucidate the biological background and to improve the detection of cancer. Therefore, we have analyzed laser-microdissected cryostat sections from head and neck tumors and adjacent mucosa on ProteinChip arrays. Two differentially expressed proteins (P = 3.34 × 10−5 and 4.6 × 10−5) were isolated by two-dimensional gel electrophoresis and identified as S100A8 (calgranulin A) and S100A9 (calgranulin B) by in-gel proteolytic digestion, peptide mapping, tandem mass spectrometry analysis, and immunodepletion assay. The relevance of these single marker proteins was evaluated by immunohistochemistry. Positive tissue areas were reanalyzed on ProteinChip arrays to confirm the identity of these proteins. As a control, a peak with low P was identified as calgizzarin (S100A11) and characterized in the same way. This technical triade of tissue microdissection, ProteinChip technology, and immunohistochemistry opens up the possibility to find, identify, and characterize tumor relevant biomarkers, which will allow the movement toward the clonal heterogeneity of malignant tumors. Taking this approach, proteins were identified that might be responsible for invasion and metastasis.

The early diagnosis of cancer at a curable stage is crucial for the successful treatment of this disease. Most of the currently used tumor assays appear too late and rely on single biomarkers with high false-negative and/or false-positive rates. As an additional burden for the patient, the traditional assays often require biopsy material instead of less invasively taken samples like serum. With the hope for more reliable DNA- and RNA-based screening tools, the research activities of the past 20 years have focused on the genomic characteristics of cancer cells. But, up to now, the output from this strategy has been disappointingly low and the disillusionment is paired with a return to proteins as the real key players in all physiological and pathological processes. Meanwhile, comparative protein profiling is generally acknowledged as a promising way for the detection of specific and predictive protein patterns reflecting certain stages of cancer without dependency on single markers. To meet the new technological demands, the ProteinChip Biomarker System was developed for the Expression Difference Mapping analysis of several hundreds of samples per day on a single, uncomplicated platform; with software support for the construction of multi-marker predictive models. The Interaction Discovery Mapping platform is introduced as the next methodical step for investigations about protein binding partners of possible importance in diagnosis and therapy. This review summarizes the current state in cancer diagnosis, provides an introduction into the ProteinChip technology, and gives an update on publications and research collaborations in SELDI-based tumor marker discovery.

Im Rahmen einer empirischen Evaluation von Mathematik-Lernpfaden an osterreichischen Schulen wurden Expertinnen und Experten sowie Lehrende und Lernende zu ausgesuchten Lernpfaden befragt. Ein wichtiges Ergebnis war, dass Lernpfade – egal ob starr linear oder flexibel im Aufbau – immer dann besonders erfolgreich waren, wenn das (interaktive) Zusammenspiel zwischen den beteiligten Lehrkraften, Schulerinnen, Schulern und der „eingebetteten“ Technik im Schulkontext gelang.

Injection of heat-killed bacteria into larvae of the greater wax moth Galleria mellonella is followed by changes in lipoprotein composition in the hemolymph. Density gradient centrifugation experiments revealed that within the first four hours after injection, a part of larval lipoprotein, high-density lipophorin (HDLp), was converted into a lipoprotein of lower density. SDS-polyacrylamide gel electrophoresis analysis of the gradient fractions and sequencing of protein fragments, established that the exchangeable apolipoprotein apolipophorin III (apoLp-III), a potent immune-activator, was associated with this newly formed lipophorin. To investigate further the influence of lipophorin-associated apoLp-III on immune-related reactions, we performed in vitro studies with isolated hemocytes from G. mellonella and lipophorins from the sphinx moth Manduca sexta, as a natural source of high amounts of low-density lipophorin (LDLp) and HDLp. The hemocytes were activated to form superoxide radicals upon incubation with LDLp, but not with HDLp. Fluorescence-labeled LDLp was specifically taken up by granular cells. This process was inhibited by adding an excess of unlabeled LDLp, but not by HDLp. We hypothesize that larval lipophorin formed in vivo is an endogenous signal for immune activation, specifically mediated by the binding of lipid-associated apoLp-III to hemocyte membrane receptors.

Apolipophorin III (apoLp-III) from the greater wax moth Galleria mellonella is an exchangeable insect apolipoprotein that consists of five amphipathic alpha-helices, sharing high sequence identity with apoLp-III from the sphinx moth Manduca sexta whose structure is available. To define the minimal requirement for apoLp-III structural stability and function, a C-terminal truncated apoLp-III encompassing residues 1-91 of this 163 amino acid protein was designed. Far-UV circular dichroism spectroscopy revealed apoLp-III(1-91) has 50% alpha-helix secondary structure content in buffer (wild-type apoLp-III 86%), increasing to essentially 100% upon interactions with dimyristoylphosphatidylcholine (DMPC). Guanidine hydrochloride denaturation studies revealed similar stability properties for wild-type apoLp-III and apoLp-III(1-91). Resistance to denaturation for both proteins increased substantially upon association with phospholipid. In the absence of lipid, wild-type apoLp-III was monomeric whereas apoLp-III(1-91) partly formed dimers and trimers. Discoidal apoLp-III(1-91)-DMPC complexes were smaller in diameter (13.5 nm) compared to wild-type apoLp-III (17.7 nm), and more molecules of apoLp-III(1-91) associated with the complexes. Lipid interaction revealed that apoLp-III(1-91) binds to modified spherical lipoprotein surfaces and efficiently transforms phospholipid vesicles into discoidal complexes. Thus, the first three helices of G. mellonella apoLp-III contain the basic features required for maintenance of the structural integrity of the entire protein.

From investigations of the vertebrate immune system gender specific differences in individual immunocompetence are well known. In general, females seem to possess more powerful immune systems than males. In invertebrates, the situation is much less clear. Therefore, we investigated the immune system of an invertebrate species, the scorpionfly Panorpa vulgaris. We found a high degree of individual variation in both traits studied, the lysozyme-like antibacterial activity of hemolymph and the capacity for in vitro phagocytosis of artificial particles. These two immune traits were positively correlated. As expected, hemolymph derived from females had higher lysozyme-like activity and hemocytes from females phagocytosed more particles. The difference in phagocytosis was mainly based on higher total hemocyte counts and higher proportions of phagocytically active cells in females, while the average number of ingested particles per active phagocyte was not significantly different. The observed gender differences are discussed in the context of reproductive strategies and parasite-mediated sexual selection.

Apolipophorin III (apoLp-III) is an exchangeable insect apolipoprotein. Its function, as currently understood, lies in the stabilization of low-density lipophorin particles (LDLp) crossing the hemocoel in phases of high energy consumption to deliver lipids from the fat body to the flight muscle cells. Recent studies with native Galleria mellonella-apoLp-III gave first indications of an unexpected role of that protein in insect immune activation. Here we report the immune activation by the recombinant protein, documenting a newly discovered correlation between lipid physiology and immune defense in insects. The complete cDNA sequence of G. mellonella-apoLp-III was identified by mixed oligonucleotide-primed amplification of cDNA (MOPAC), 3'-RACE-PCR, and cRACE-PCR. The sequence coding for the native protein was ligated into a pET-vector; this construct was transfected into Escherichia coli and overexpressed in the bacteria. Photometric turbidity assays with human low density lipoprotein (LDL) and transmission electron microscopy studies on apoLp-III-stabilized lipid discs revealed the full functionality of the isolated recombinant apoLp-III with regard to its lipid-association ability. For proving its immune-stimulating capacity, apoLp-III was injected into the hemocoel of last instar G. mellonella larvae and the antibacterial activity in cell-free hemolymph was determined 24 h later. As a result, the hemolymph samples of injected insects contained strongly increased antibacterial activities against E. coli as well as clearly enhanced lysozyme-like activities. From Northern blot analysis of total RNA from insects injected with apoLp-III or the bacterial immune provocator lipopolysaccharide, it could be concluded that the transcription rate of apoLp-III mRNA does not vary in comparison to untreated last instar larvae.

Background: Alzheimer’s disease (AD) is characterized by β-amyloid (Aβ) peptide-containing plaques and tau-containing neurofibrillary tangles. By intracerebral injection of Aβ42, both pathologies have been combined in P301L tau mutant mice. Furthermore, in cell culture, Aβ42 induces tau aggregation. While both Aβ42 and mutant tau cause neuronal dysfunction, their modes of action are only vaguely understood. Methods: To determine which processes are disrupted by Aβ42 and/or P301L mutant tau, we used transcriptomic and proteomic techniques followed by functional validation and analysis of human AD tissue. Results: Our transcriptomic study in the SH-SY5Y cell culture system revealed that Aβ42 and P301L tau expression independently affect genes controlling the cell cycle and cell proliferation. Proteomics applied to Aβ42-treated P301L tau-expressing SH-SY5Y cells and the amygdala of Aβ42-injected P301L transgenic mice revealed that a significant fraction of proteins altered in both systems belonged to the same functional categories, i.e. stress response and metabolism. Among the proteins identified was valosin-containing protein (VCP), a component of the quality control system during endoplasmic reticulum stress. Mutations in VCP have recently been linked to frontotemporal dementia. Conclusion: Our data support the mitosis failure hypothesis that claims that aberrant cell cycle reentry of postmitotic neurons induces apoptosis. Furthermore, our data underline a role of Aβ42 in the stress response associated with protein folding.

Apolipophorin III (apoLp-III) was isolated from the haemolymph of last instar larvae of Galleria mellonella. The ultraviolet (u.v.) spectrum and the N-terminal amino acid sequence reveal high similarities with the apoLp-III from Manduca sexta. The protein is heat-stable. The molecular mass of apoLp-III was determined to be 18 077 Da using mass spectrometry. The heat treatment (90 degrees C, 30 min) resulted in a pI shift from 6.6 for the non-heated to 6.1 for the heat-treated apoLp-III without change in the molecular mass, indicating that a conformational change might have been caused by the heat treatment, rather than covalent alterations. Intrahaemocoelic injection of pure apoLp-III into last instar G. mellonella larvae is followed by a dose-dependent increase of antibacterial activity in cell-free haemolymph of treated larvae 24 h after injection. Furthermore, pure apoLp-III enhances the phagocytic activity of isolated haemocytes in vitro. The newly discovered role of apoLp-III in inducing immune-related functions in insects is discussed in regard to the known features of this molecule in lipid metabolism. Arylphorin, another heat-stable protein in G. mellonella haemolymph, was likewise isolated in this study. The protein was identified by N-terminal protein sequencing, the sequence obtained exactly matches the known sequence data for this protein. Copyright 1997 Elsevier Science Ltd. All rights reserved

Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) represents the successful combination of retentate chromatography and mass spectrometry, and this technology is an integral part of Ciphergen's ProteinChip System, which was designed to answer biomedical questions by performing protein analyses on a single experimental platform. The quantification capability of the ProteinChip System is essential in all proteomic applications for which this technology is used. Here we describe methods and results for three short experiments mimicking realistic analytical challenges to provide practical examples of quantification.

We established an in vitro transfer system with monolayers of isolated plasmatocytes from Galleria mellonella. The plasmatocytes represent the main phagocytically active haemocyte type in this lepidopteran insect. Plasmatocytes to which hydrophilic silica beads were added as a phagocytosing agent served as ‘donor’ cells. Supernatants from these donor cultures were transferred to freshly prepared ‘recipient’ plasmatocyte monolayers. Subsequently, FITC (fluorescein-isothiocyanate) labelled yeast cells were added to the recipient monolayers and the phagocytic activity was determined using an FITC quenching assay with trypan blue. The phagocytic activity in plasmatocyte monolayers which received supernatants from phagocytically active donor cells was significantly higher than the activity of cells receiving supernatants from non-activated donor cells. Time course studies revealed that the inducing capacity of the donor cell supernatants was highest 2–4h after starting phagocytosis of the silica beads. Isolation of the responsible phagocytosis stimulating factor is still underway. From our investigations we can conclude that it must be a very small (

An in vitro microscopic fluorescence assay determining the phagocytic activity of isolated plasmatocytes of Galleria mellonella is described. It was developed to quantify insect cellular immune reactions. The assay, a modification of a method originally established for vertebrate blood cells, is based on the quenching effect of trypan blue on fluorescein-isothiocyanate-labelled yeast cells. Only ingested yeast cells retain their fluorescence after quenching and can be easily distinguished from adhering ones. The technique is highly reproducible and easy to perform. Using this method a phagocytosis-stimulating effect caused by a haemolymph fraction > 100 kDa isolated from G. mellonella is demonstrated.

Intrahaemocoelic injection of silica beads into Galleria mellonella (wax moth) larvae provoked strong cellular and humoral reactions similar to those normally occuring during an antibacterial defence. The cellular reactions of the haemocytes—investigated by light and scanning electron microscopy—comprised degranulation of granular cells and phagocytosis by plasmatocytes. The humoral responses—measured in cell free haemolymph as the increase of antibacterial activity against Echerichia coli K12 D31 and of lysozyme activity against Micrococcus luteus cell walls—were significantly enhanced in comparison to controls. Only hydrophylic but not hydrophobic silica beads provoked strong reactions. Plasmatocytes (PLs), the main phagocytic haemocytes of G. mellonella, were isolated by using a newly adapted nylon wool column technique. PL monolayers, prepared from isolated cells, exhibited a high purity by consisting of at least 90% PL. Scanning electron microscopy studies revealed that 64% of the isolated PLs showed phagocytic activity against the sterile silica beads in vitro. Intrahaemocoelic injection of supernatants from monolayers with phagocytosing plasmatocytes into naive larvae led to a clearly higher antibacterial activity against E. coli in haemolymph of recipients than the injection of supernatants from monolayers with non-phagocytosing cells. The earlier supposition that haemocyte-released factors induce the humoral immune response is further supported by these results.

Facing global competition in the chemical industry particular companies from high-wage countries have to cut development costs and time to market to be still profitable. Therefore, methods like concurrent and collaborative engineering are increasingly applied. However, these complex workflows require adequate software support to be efficient in face of heterogeneous software environments as typically encountered in most companies. Such software support does virtually not exist in industrial practice to date. In this paper, we propose a novel software prototype built on semantic technologies which is capable of providing such software support and thus helping to improve efficiency in process and plant engineering.

Injection of ion exchange beads or sterile latex beads into the haemocoel of wax moth ( Galleria mellonella ) larvae provokes an humoral immune response measurable as antibacterial activity in cell-free haemolymph. The influence of provocator surface properties on the intensity of response was investigated. Comparing the antibacterial activities provoked by injection of anion and cation exchangers it can be concluded, that anion exchangers are better provocators than cation exchangers. The influence of physicochemical parameters was confirmed by the fact, that injection of latex beads pretreated with sulphuric acid lead to enhanced antibacterial activities in larvae as compared to the activities provoked by injection of untreated beads. In order to prove if it is possible to enhance the provocation capacity of beads by binding molecules to their surfaces, the following substances were covalently coupled onto the beads prior to injection: fibronectin, peptides with a cell adhesive signal of fibronectin (GLY-ARG-GLY-ASP-SER-PRO-LYS, GLY-ARG-GLY-ASP-SER, ARG-GLY-ASP-SER), poly-lysine, adjuvant peptide, lysozyme, bovine serum albumin, bovine plasma, cell-free haemolymph and haemolymph lysate supernatant (haemolymph preparations from G. mellonella ) Coupling of adjuvant peptide, fibronectin or haemolymph preparations enhanced the provocation capacity of beads very clearly. Likewise, but to a lower extent, an enhancement was noticed for nearly all the other substances tested in comparison to results obtained by injection of unloaded beads. The results will be discussed in relation to the known facts about the influence of provocator characteristics onto the onset of a cellular reaction by arthropod and vertebrate cells.

Having established the scientific background of ontology engineering, we now present version 2.0 of the ontology OntoCAPE. Compliant with the terminology introduced in the previous chapter, OntoCAPE can be characterized as a formal, heavyweight ontology, which is represented in the OWL modeling language. It consists of several sub-ontologies, which perform different functions: According to the classification framework introduced in Sect. 2.6, the individual sub-ontologies serve the functions of a meta ontology (at the logical metalevel), a top-level ontology, a domain ontology, as well as some application ontologies.

Chemical_process_system is the key partial model in the ontology which addresses the body of knowledge of the chemical engineering discipline. However, it is not intended to function as a textbook or handbook for this discipline. Primarily, this partial model is aimed to present an organization of chemical engineering knowledge, by means of positioning, grouping, and linking chemical engineering concepts within a number of ontology modules. The descriptions or definitions of individual concepts presented in this partial model are all serving this purpose; more rigorous and comprehensive explanations of these concepts should not be sought in this section or in this ontology, but rather in the specialized textbooks or handbooks.

This chapter gives an overview on the information models and ontologies that are thematically related to OntoCAPE. It is structured into two major parts: Section 11.1 reviews the previous work in the research group of the authors; that is, the information models preceding OntoCAPE are described, and the progress made over time is discussed. In Sect. 11.2, the work of other research groups is analyzed and compared against OntoCAPE.

In this chapter, some prototypical software applications are presented, which have been created by the authors’ colleagues within the research projects COGents and IMPROVE. What all prototypes have in common is that their respective implementations are based on OntoCAPE. While these prototypes are of interest in themselves, they are presented here primarily for other reasons: that is, (a) to demonstrate the practical usability and reusability of OntoCAPE, and (b) to highlight the gradual improvement of the different versions of OntoCAPE, which have been triggered by implementations in different application contexts. Therefore, the descriptions of the different prototypes are intentionally kept short; detailed accounts of these have been published elsewhere, as will be indicated by appropriate references.

Concluding the description of OntoCAPE, we will subsequently present the major principles according to which the ontology has been designed. Basically, design principles are objective criteria for guiding and evaluating the design decisions made during ontology development (Gruber 1995). A number of design principles for information modeling in general, and ontology engineering in particular, have been suggested in the literature (e.g., Gruber 1995; Fox and Gruninger 1998; Arpirez et al. 1998; Chandrasekaran et al. 1999; Gomez-Perez et al. 2004; Rector et al. 2004; Smith 2006; and others). Compliance with these acknowledged principles is a credible indicator for the quality of an ontology.

This work shows for the first time the presence of erratic phenomena in p-channel floating gate memories using Fowler Nordheim tunneling for both program and erase operations. A specific p-channel EEPROM architecture is investigated and found to be intrinsically robust against erratic behaviors. A comparison between the p-channel device and a conventional n-channel Flash is discussed and physical interpretations are suggested.

This article presents substantial results from two projects that deal with teaching and learning with digital media in basic and higher education and offers a new perspective on the active role of technology in learning processes. The first case draws on the project “Roberta—girls conquer robotics,” which was launched by the Fraunhofer Institute (AIS) with the aim to help promote girls’ interest in sciences, mathematics and technology. It suggests a new pedagogical approach towards the use of robotics in education and discusses how didactics and technology (LegoMindstorms) interact and how the character of robotics itself plays an important role here, such as it already comes along as gendered material. The second case focuses on distance education teaching methods in childcare management. The space left for practitioners in Higher Education is either to embrace the new media or to watch its inevitable unfolding. We take a critical stance towards that perspective and suggest that the shape and learning effect of new media in higher education is contested and evolves in communities of practice. No technologies are neutral and it is more appropriate to speak of technological and societal features as interactively fostering e-learning processes through distributed actions (Rammert, 2002).

The cultural and technical history of e-learning scenarios can be traced back to traditional forms of distance studies, CD-Rom learning programmes, audio-programmes or educational TV. But other than these forerunners, two closely related myths often shape policy towards ICT and education: the irresistible power of globalisation and the determining effect of technology. Both views present the success of e-learning throughout the education system as inevitable. The space left for practitioners in higher education is either to embrace the new media or to watch its inevitable unfolding. In this paper we take a critical stance towards that perspective and suggest that the shape and learning effect of new media in higher education is contested and evolves in communities of practice. No technologies are neutral and it is more appropriate to speak of economic, technological and societal features as interactively fostering the importance of e-learning through distributed actions (Rammert, 2002). From such a perspective, e-learning is perceived as a co-product of didactically and technically situated features (Wiesner-Steiner, Wiesner, & Schelhowe, 2006) that foster and enable but don`t determine human learning through the use of digital technologies. Main characteristics are: • Interactive and multimedial design of content • Learning via digital networks • Netbased communication The EU-Leonardo-project “European Enhancement of Early Years Management Skills—EEEYMS” (http://www. eeeyms.org/) was intended to enhance employability of people employed in the Early Years Childcare management sector by providing access to a high level qualification in line with the emerging industry requirements. This was achieved by developing distance learning materials available via the World Wide Web and other forms of media including CDRom` s, specific to the employment area which is also aligned to a degree pathway, and will be available within Europe. It was further achieved by the creation of a European network association for childcare to ensure sustainability after the project is complete. EEEYMS provides an accredited route for the attainment of a relevant degree level qualification for careers and managers within the childcare sector, and assist in attracting suitable people into this employment sector to meet the childcare demand over the next 10 years. With ODL materials, the project enhances employment opportunities and career status for a still predominantly female workforce. Research suggests that the increased status and professionalisation obtained through the availability of a high level qualification will make the industry more attractive to male employees. EEEYMS thus provided higher level qualification to people disadvantaged in the labour market and those who faced discrimination in accessing training due to disability, geographical location or family commitments. The use of ICT systems was thus thought to enhance knowledge and learning experience and the employability factors, as the knowledge will be directly transferable to the work environment.

Information integration during the design process of chemical plants is a long-standing and not sufficiently solved problem in industrial practice to date. The major challenge identified is the capturing of the information's semantics. Within an ongoing research project an ontology-based approach for information integration in process engineering design projects is developed. This contribution sketches the semantic information model applied in the integration software, which is based on the formal ontology OntoCAPE.

Qualifying a high temperature, high endurance and high reliability integrated EEPROM process module according the JEDEC and AEC standard needs a large number of tested devices. Correlations of various analog and digital measurements must be done at different supply voltages, temperature conditions and with process variations to ensure a stable high yielding process module. Long program and erase times (milliseconds) for an EEPROM process option result in time consuming measurements. The costs of such a qualification will be comparatively high if all tests are done with production test equipment. Therefore, a test chip concept allowing a wide range of memory sizes was defined for use with a standard PLCC68 package. This package is able to withstand temperatures up to 180degC. Based on the test chip, a parallel, low cost test system was developed enabling the measurement of 96 devices in parallel and hence significantly reducing the test and qualification time and costs.

which express either the 4-repeat tau domain with the FTDP-17 mutation Delta-K280 (TauRD/DeltaK280 “pro-aggregation mutant”) or the 4-repeat tau domain with Delta-K280 deletion and two proline mutations in the hexapeptide motifs (TauRD/DeltaK280/I277P/I308 “antiaggregation mutant”). Results: The DeltaK280 mutation accelerates the aggregation of tau, but the inserted proline residues inhibit the tau aggregation in vitro and in cell models. Inducible transgene expression in mice was driven by a forebrain-specific CaMKII promoter in a Tet-Off system and can be suppressed by doxycycline. The pro-aggregation mutant showed aggregated tau in sarkosyl insoluble fractions and Gallyas silver stained neurofibrillary tangles from 3 months onwards, even though the level of the human tau protein was lower than endogenous mouse tau. Tau preparations from pro-aggregation mutant mice revealed PHFs by electron microscopy. Consistent with the tau pathology the neuronal loss was age-dependent and visible in the dentate gyrus as early as 5 months. The immunohistochemisty results showed phosphorylated tau at S262 missorted into the somatodendritic compartment of cortical and hippocampal neurons. The anti-aggregation mutant with a similar expression level as the pro-aggregation mutant did not show aggregated tau or neuronal loss, but missorting into the somatodendritic compartment. The level of synaptophysin, a presynaptic marker and the number of spine-synapses were reduced in the stratum radiatum of the pro-aggregation mutant, but not of the antiaggregation mutant. Six weeks of switching off the tau transgene in the pro-aggregation mutant lead to 90% reduction in the level of soluble human tau protein, to complete reversal of the pathological somatodendritic localization and of phosphorylation in the repeat domain. Remarkably, the aggregation was only partly reversed. The remaining aggregates did not contain the exogenous human tau, but the endogenous mouse tau. Conclusions: The results argue that a toxic species of tau, once introduced into neurons, can “poison” endogenous tau and propagate its aggregation for extended time periods. Supported by MPG and DFG.

The project “Roberta – girls conquer robotics” was launched by the Fraunhofer Institute (AIS) with the aim to help promote girls’ interest in sciences, mathematics and technology. As a summary of this research program, this article presents substantial results from the scientific evaluation of Roberta and suggests a new pedagogical approach towards the use of robotics in education. We discuss how didactics and technology (LegoMindstorms) interact in Roberta courses and how the materiality of robotics itself plays an important role here; that is, it already comes along as gendered material. Due to that, we draw conclusions towards general educational concepts for digital media. If carefully used as a didactical actor, robotics not only suits boys’ and girls’ interest in technological messiness but enables them for a technological-mediated life instead of just feeling overwhelmed. Robotics, therefore, can function as an appropriate medium for general education in the more comprehensive sense of developing personality and agency.

In this contribution a novel investment planning model for the development of stepwise capacity expansion strategies for chemical plants is proposed. This method is implemented in a decision support tool that can be, used during the early stage of plant engineering — a phase which is concerned with the conversion of a chemical process into a highly profitable plant. Based on a previous work by Oldenburg et al. [1], who proposed a method for a quick economic comparison of possible stepwise plant expansion scenarios versus building a full capacity plant, the approach presented in this paper is capable of identifying the optimal process-specific investment strategy on the level of unit operations. A mixed-integer linear programming model dedicated for stepwise capacity expansion strategies for chemical process plants forms the core of the tool.