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This work studies the particle exchange rates in horizontal fluidized beds equipped with different weir designs between compartments. These particle exchange rates provide information on the axial dispersion of the solid material within the process. For this purpose discrete particle modelling (DPM) was used to determine the particle exchange on microscopic level. This method uses a coupled CFD-DEM approach to observe particle dynamics in a fluid field. The model was validated against exchange rates in a lab-scale setup as determined by Particle Tracking Velocimetry (PTV) with very good quantitative agreement, showing the suitability of the method for the evaluation of weir designs. Simulations were performed for different weir designs and under variation of the hold-up mass, the feed rate and gas velocity to predict their transport behavior in a pilot-scale 3D horizontal fluidized bed. The results indicate that the solids transport behavior is strongly dependent on the used weir design and the main driving force for the particle transport that can be influenced by the process conditions. The installation of weirs between two compartments induces a transport resistance, while the base type without the installation of a weir between the two chambers represents the fastest possibility for mixing the particles of a two-compartment system. It has been observed that the general trend shows higher particle recirculation rates for the overflow weir and base configuration (no weir), whereas the underflow and sideflow weir applications improve the solids transport through the horizontal fluidized bed.

This work focuses on continuously operated spray granulation processes in horizontal fluidized beds highlighting the influence of process conditions on the particle properties of the resulting product granules. The drying process has a decisive influence on the kinetics of the growth rate and thus also on the properties of the particles, such as the morphological structure, particle moisture content and porosity as well as density, compression strength and the wetting behavior. This influence has been considered in this study in more detail on the basis of the model material sodium benzoate. In order to compare the produced granules at different drying conditions and spray rates of the suspension an external product classification was used to achieve a certain product granule size. The obtained experimental results show a deep influence of the thermal conditions onto granule morphology and structural properties, which is in qualitative agreement with recent experimental observations (Rieck et al., 2015; Hoffmann et al., 2015a , Schmidt et al., 2017b ). The overall trend of the results reveal smoother product granules with decreasing spray rates of the suspension and increasing drying temperatures. These smoother surface morphologies lead to a more homogeneous layering which has as a consequence that the internal particle porosity is decreasing while the solids density and the compression strength of the particles are increasing at the same time. In this study the purely qualitative classification of the surface texture from previous experimental studies was extended by the topographic analysis of the product granules, giving the possibility to quantify the morphological structure by means of roughness measurements. This makes the morphological design accessible as product property and permits the utilization of models that describe the morphology according to the process conditions.

Research into the regulation of gene expression underwent a shift from focusing on DNA-binding proteins as key transcriptional regulators to RNA-binding proteins (RBPs) that come into play once transcription has been initiated. RBPs orchestrate all RNA-processing steps in the cell. To obtain a global view of in vivo targets, the RNA complement associated with particular RBPs is determined via immunoprecipitation of the RBP and subsequent identification of bound RNAs via RNA-seq. Here, we describe technical advances in identifying RBP in vivo targets and their binding motifs. We provide an up-to-date view of targets of nucleocytoplasmic RBPs collected in arabidopsis. We also discuss current experimental limitations and provide an outlook on how the approaches may advance our understanding of post-transcriptional networks.

Residence time distributions (RTDs) in horizontal fluidised beds have a huge effect on solid product properties and are influenced by the internal design of the apparatus, e.g. the separation into different compartments by weirs. Weirs can be passed in or against the overall solid transport direction, with the back-flow resulting in axial dispersion, which is a measure of the spread of the RTD. Therefore, the ratio of exchange rates at weirs under different fluidisation conditions provides information on axial dispersion. In this work, a methodology based on particle tracking velocimetry is presented to obtain information on the exchange rates of particles at weirs in horizontal fluidised beds. The internal recirculation is studied for over-flow weirs with respect to different fluidisation conditions, providing a first step towards determining the effects of weirs and fluidisation conditions on axial dispersion and RTDs in horizontal fluidised beds.

Several studies—theoretical and experimental—show that continuous fluidised bed layering granulation with external classification can show instability in the form of self-sustained oscillations. Recent results show that the process stability does not only depend on product-related process parameters but also on the formation of functional zones in the fluidised bed chamber, especially the formation of a spray and drying zone. In this work a systematic evaluation of zone formation in different apparatus designs (e.g., top- and bottom-spray in cylindrical apparatuses) and its influence on process stability is performed, resulting in a stability regime map for the different apparatus designs and key operation parameters.

Problem- und Zielstellung Gesundheit gilt als zentrale Voraussetzung der Arbeitsfahigkeit (Af). Aussagen zur Lehrergesundheit basieren uberwiegend auf Selbstberichten, aber kaum auf physiologischen Gesundheitsdaten. Der Vergleich zur Bevolkerung steht aus. Zu klaren ist, inwieweit sich Lehrkrafte (LK) in ihrer Af, physischen Gesundheit und Verhaltensmerkmalen von anderen Erwerbstatigen (regionale Erwerbstatigenstichprobe – rESP) unterscheiden (1) und welche Gesundheits- und Verhaltensmerkmale die Af der LK und rESP beeinflussen (2).

Eine innere Uhr synchronisiert den Tagesablauf der Pflanze mit dem Tag-Nacht-Rhythmus. In jeder Pflanzenzelle tickt ein molekulares Uhrwerk, das durch den Licht-Dunkel-Wechsel getaktet wird. Bisher gingen die Chronobiologen davon aus, dass die Uhren in den einzelnen Pflanzenzellen unabhangig voneinander gehen. Neuere Arbeiten an der Modellpflanze Arabidopsis thaliana haben nun gezeigt, dass die innere Uhr der Blatter etwas anders aufgebaut ist als die innere Uhr in den Wurzeln und diese sogar steuert. Auch innerhalb eines Blattes sind die Zellen in verschiedenen Zelltypen, den Mesophyllzellen, den Zellen der Epidermis und den Zellen des Leitgewebes unterschiedlich, und die Uhr im Leitgewebe gibt den Uhren in den Mesophyllzellen den Takt vor. Somit scheint es im Uhrensystem der Pflanze eine Hierarchie zu geben. Eine solche Rangordnung war bisher nur von Tier und Mensch bekannt mit dem ubergeordneten Steuerzentrum im Gehirn und galt als ein fundamentaler Unterschied in der Organisation des Zeitmess-Systems. Hierarchy in the plant clock shop Higher plants use an endogenous timekeeper, the circadian clock, to adjust to the periodic changes in light and darkness in their environment. It has long been assumed that plant cellular clocks act as stand-alone systems. Recent evidence points to widespread coupling among clocks in different organs and different cells. Moreover, a hierarchy has been observed between clocks in leaves and roots and even between clocks in individual cell types of the leaf, with the clock in the vasculature being dominant over the clock in mesophyll cells. Thus, the plant circadian system may also show a hierarchical organization reminiscent of the clock system in mammals.

Thyroid hormones (THs) are transported across cell membranes by different transmembrane transporter proteins. In previous studies, we showed marked 3,3′-diiodothyronine (3,3′-T2) but moderate T3 uptake by the L-type amino acid transporter 2 (Lat2). We have now studied the structure-function relationships of this transporter and TH-like molecules. Our Lat2 homology model is based on 2 crystal structures of the homologous 12-transmembrane helix transporters arginine/agmatine antiporter and amino acid/polyamine/organocation transporter. Model-driven mutagenesis of residues lining an extracellular recognition site and a TH-traversing channel identified 9 sensitive residues. Using Xenopus laevis oocytes as expression system, we found that side chain shortening (N51S, N133S, N248S, and Y130A) expanded the channel and increased 3,3′-T2 transport. Side chain enlargements (T140F, Y130R, and I137M) decreased 3,3′-T2 uptake, indicating channel obstructions. The opposite results with mutations maintaining (F242W) or impairing (F242V) uptake suggest that F242 may have a gating function. Competitive inhibition studies of 14 TH-like compounds revealed that recognition by Lat2 requires amino and carboxylic acid groups. The size of the adjacent hydrophobic group is restricted. Bulky substituents in positions 3 and 5 of the tyrosine ring are allowed. The phenolic ring may be enlarged, provided that the whole molecule is flexible enough to fit into the distinctly shaped TH-traversing channel of Lat2. Taken together, the next Lat2 features were identified 1) TH recognition site; 2) TH-traversing channel in the center of Lat2; and 3) switch site that potentially facilitates intracellular substrate release. Together with identified substrate features, these data help to elucidate the molecular mechanisms and role of Lat2 in T2 transport.

Im Rahmen des Projektes AnschlussM wurden 1525 LehrerInnen und ErzieherInnen in Bremen und Baden-Württemberg zu ihren epistemologischen Überzeugungen zur Natur von Mathematik, zum Lehren und Lernen von Mathematik und zur Natur mathematischer Leistungen befragt. Es zeigen sich durchgehend signifikante Unterschiede nicht nur zwischen LehrerInnen und ErzieherInnen, sondern auch zwischen LehrerInnen mit einem Fachstudium in Mathematik und LehrerInnen ohne Mathematikstudium derart, dass LehrerInnen mit einem Fachstudium in Mathematik sich eindeutiger zu den Überzeugungen zur Mathematik positionieren, sei es in einer deutlicheren Ablehnung oder Zustimmung. Unterschiede zwischen den Bundesländern sind nur im Einzelfall zu beobachten.

In this work a generic multi-compartment, multi-zone population balance model (PBM) is developed which allows predicting the process dynamics of particle formation in a horizontal fluidized bed. It focuses on the particle size distribution (PSD) which is an important quality parameter in solids process industry. It is influenced by different factors, e.g. apparatus design (weir and nozzle assembly) and process conditions (mass flow rate), respectively. In this study the apparatus design by an over and under flow weir configuration, used separately or in combination, is investigated to obtain the product properties at the outlet of the apparatus. Simulation results show how characteristic product data depend on the process conditions and apparatus design. The obtained trends can then be used for an inverse apparatus design of horizontal fluidized beds to obtain particles with desired properties.

Background Functions for RNA-binding proteins in orchestrating plant development and environmental responses are well established. However, the lack of a genome-wide view of their in vivo binding targets and binding landscapes represents a gap in understanding the mode of action of plant RNA-binding proteins. Here, we adapt individual nucleotide resolution crosslinking and immunoprecipitation (iCLIP) genome-wide to determine the binding repertoire of the circadian clock-regulated Arabidopsis thaliana glycine-rich RNA-binding protein AtGRP7. Results iCLIP identifies 858 transcripts with significantly enriched crosslink sites in plants expressing AtGRP7-GFP that are absent in plants expressing an RNA-binding-dead AtGRP7 variant or GFP alone. To independently validate the targets, we performed RNA immunoprecipitation (RIP)-sequencing of AtGRP7-GFP plants subjected to formaldehyde fixation. Of the iCLIP targets, 452 were also identified by RIP-seq and represent a set of high-confidence binders. AtGRP7 can bind to all transcript regions, with a preference for 3′ untranslated regions. In the vicinity of crosslink sites, U/C-rich motifs are overrepresented. Cross-referencing the targets against transcriptome changes in AtGRP7 loss-of-function mutants or AtGRP7-overexpressing plants reveals a predominantly negative effect of AtGRP7 on its targets. In particular, elevated AtGRP7 levels lead to damping of circadian oscillations of transcripts, including DORMANCY/AUXIN ASSOCIATED FAMILY PROTEIN2 and CCR-LIKE. Furthermore, several targets show changes in alternative splicing or polyadenylation in response to altered AtGRP7 levels. Conclusions We have established iCLIP for plants to identify target transcripts of the RNA-binding protein AtGRP7. This paves the way to investigate the dynamics of posttranscriptional networks in response to exogenous and endogenous cues. Electronic supplementary material The online version of this article (doi:10.1186/s13059-017-1332-x) contains supplementary material, which is available to authorized users.

Die Untersuchung analysiert Zusammenhange zwischen Dimensionen (trans-) professioneller Kooperation und padagogischen Arbeitsbedingungen in einem bundeslanderubergreifenden Vergleich. Die empirische Basis liefert AnschlussM, welches 1.525 Fachkrafte aus Kindergarten und Grundschule in Baden-Wurttemberg und Bremen befragte.

The hnRNP-like glycine-rich RNA-binding protein AtGRP7 regulates pre-mRNA splicing in Arabidopsis. Here we used small RNA-seq to show that AtGRP7 also affects the miRNA inventory. AtGRP7 overexpression caused a significant reduction in the level of 30 miRNAs and an increase for 14 miRNAs with a minimum log2 fold change of ±0.5. Overaccumulation of several pri-miRNAs including pri-miR398b, pri-miR398c, pri-miR172b, pri-miR159a and pri-miR390 at the expense of the mature miRNAs suggested that AtGRP7 affects pri-miRNA processing. Indeed, RNA immunoprecipitation revealed that AtGRP7 interacts with these pri-miRNAs in vivo. Mutation of an arginine in the RNA recognition motif abrogated in vivo binding and the effect on miRNA and pri-miRNA levels, indicating that AtGRP7 inhibits processing of these pri-miRNAs by direct binding. In contrast, pri-miRNAs of selected miRNAs that were elevated or not changed in response to high AtGRP7 levels were not bound in vivo. Reduced accumulation of miR390, an initiator of trans-acting small interfering RNA (ta-siRNA) formation, also led to lower TAS3 ta-siRNA levels and increased mRNA expression of the target AUXIN RESPONSE FACTOR4. Furthermore, AtGRP7 affected splicing of pri-miR172b and pri-miR162a. Thus, AtGRP7 is an hnRNP-like protein with a role in processing of pri-miRNAs in addition to its role in pre-mRNA splicing.

RNA-protein interaction is an important checkpoint to tune gene expression at the RNA level. Global identification of proteins binding in vivo to mRNA has been possible through interactome capture - where proteins are fixed to target RNAs by UV crosslinking and purified through affinity capture of polyadenylated RNA. In Arabidopsis over 500 RNA-binding proteins (RBPs) enriched in UV-crosslinked samples have been identified. As in mammals and yeast, the mRNA interactomes came with a few surprises. For example, a plethora of the proteins caught on RNA had not previously been linked to RNA-mediated processes, for example proteins of intermediary metabolism. Thus, the studies provide unprecedented insights into the composition of the mRNA interactome, highlighting the complexity of RNA-mediated processes.

Animations presented at different speed are assumed to differentially interact with learners’ perception and cognition due to the constraints imposed by learners’ limited sensitivity to incoming dynamic information. To investigate the effects of high and low presentation speed of animation, two studies were conducted. In Study 1, participants were 55 students who learned about the functioning of a four-stroke engine from an animation with user-controlled presentation speed. In Study 2, eye movements of 19 students were analysed for different system-controlled presentation speeds of animation. Results indicated that high presentation speeds accentuated global events (i.e., macro-events), whereas low speeds accentuated local events (i.e., micro-events). However, eye movements were primarily affected by the content rather than the presentation speed of animation.

Measurement of the electrochemical properties phase-by-phase on the nanoscale in real (commercial) alloys is critical to understanding the microstructure-corrosion relationship and subsequently controlling it. This work presents a novel AFM based in situ corrosion probing methodology (for the first time) that is capable of resolving the electrochemical activity (impedance response) into the nanometer range; the method subsequently having major ramifications in the study of aluminium alloy corrosion, the interpretation of corrosion propagation, and the subsequent development of corrosion resistant aluminium alloys.

Eukaryotic cells have to prevent the export of unspliced pre-mRNAs until intron removal is completed to avoid the expression of aberrant and potentially harmful proteins. Only mature mRNAs associate with the export receptor Mex67/TAP and enter the cytoplasm. Here we show that the two shuttling serine/arginine (SR)-proteins Gbp2 and Hrb1 are key surveillance factors for the selective export of spliced mRNAs in yeast. Their absence leads to the significant leakage of unspliced pre-mRNAs into the cytoplasm. They bind to pre-mRNAs and the spliceosome during splicing, where they are necessary for the surveillance of splicing and the stable binding of the TRAMP complex to spliceosome-bound transcripts. Faulty transcripts are marked for their degradation at the nuclear exosome. On correct mRNAs the SR proteins recruit Mex67 upon completion of splicing to allow a quality controlled nuclear export. Altogether, these data identify a role for shuttling SR proteins in mRNA surveillance and nuclear mRNA quality control.

A generic multi-compartment, multi-zone population balance model (PBE) is developed. The model considers particle properties as well as the geometric coordinates (apparatus length). Further features of the presented model are the possibility to include different transport mechanisms from one process chamber to the next, the possibility of arbitrary positions of particle recycle as well as different operating conditions in each chamber. By parametric studies the influence of important process parameters on the product quality is investigated. It is the aim of this work to link product properties, in particular the particle size distribution, to a multi-zone model that can be readily applied in an industrial environment for process design and optimization.

Lichen planopilaris (LPP) is a chronic inflammatory disease of unknown pathogenesis that leads to permanent hair loss. Whilst destruction of epithelial hair follicle stem cells (eHFSCs) that reside in an immunologically protected niche of the HF epithelium, the bulge, is a likely key event in LPP pathogenesis, this remains to be demonstrated. We have tested the hypotheses that bulge immune privilege (IP) collapse and inflammation-induced eHFSC death are key components in the pathogenesis of LPP. Biopsies of lesional and non-lesional scalp skin from adult LPP patients (n = 42) were analysed by quantitative (immuno)histomorphometry, real-time quantitative polymerase chain reaction (qRT-PCR), laser capture microdissection and microarray analysis, or skin organ culture. At both the protein and transcriptional level, lesional LPP HFs showed evidence for bulge IP collapse (ie increased expression of MHC class I and II, β2microglobulin; reduced TGFβ2 and CD200 expression). This was accompanied by a Th1-biased cytotoxic T cell response (ie increased CD8(+) GranzymeB(+) T cells and CD123(+) plasmacytoid dendritic cells, with increased CXCR3 expression) and increased expression of interferon-inducible chemokines (CXCL9/10/11). Interestingly, lesional LPP eHFSCs showed both increased proliferation and apoptosis in situ. Microarray analysis revealed a loss of eHFSC signatures and increased expression of T cell activation/binding markers in active LPP, while bulge PPARγ transcription was unaltered compared to non-lesional LPP HFs. In organ culture of non-lesional LPP skin, interferon-γ (IFNγ) induced bulge IP collapse. LPP is an excellent model disease for studying and preventing immune destruction of human epithelial stem cells in situ. These novel findings raise the possibility that LPP represents an autoimmune disease in whose pathogenesis IFNγ-induced bulge IP collapse plays an important role. Therapeutically, bulge IP protection/restoration may help to better manage this highly treatment-resistant cicatricial alopecia.

The genus Octadecabacter is a member of the ubiquitous marine Roseobacter clade. The two described species of this genus, Octadecabacter arcticus and Octadecabacter antarcticus, are psychrophilic and display a bipolar distribution. Here we provide the manually annotated and finished genome sequences of the type strains O. arcticus 238 and O. antarcticus 307, isolated from sea ice of the Arctic and Antarctic, respectively. Both genomes exhibit a high genome plasticity caused by an unusually high density and diversity of transposable elements. This could explain the discrepancy between the low genome synteny and high 16S rRNA gene sequence similarity between both strains. Numerous characteristic features were identified in the Octadecabacter genomes, which show indications of horizontal gene transfer and may represent specific adaptations to the habitats of the strains. These include a gene cluster encoding the synthesis and degradation of cyanophycin in O. arcticus 238, which is absent in O. antarcticus 307 and unique among the Roseobacter clade. Furthermore, genes representing a new subgroup of xanthorhodopsins as an adaptation to icy environments are present in both Octadecabacter strains. This new xanthorhodopsin subgroup differs from the previously characterized xanthorhodopsins of Salinibacter ruber and Gloeobacter violaceus in phylogeny, biogeography and the potential to bind 4-keto-carotenoids. Biochemical characterization of the Octadecabacter xanthorhodopsins revealed that they function as light-driven proton pumps. peerReviewed

Purpose To assess the outcome of multi-catheter pulse dose rate (PDR) brachytherapy of re-irradiation for local ipsilateral breast tumour recurrence (IBTR) in regard to local control, survival, morbidity and quality of life (QoL). Patients and methods Between 1999 and 2006, 39 patients were included with histologically confirmed IBTR, Karnofsky index ⩾80% and refusal of mastectomy. Exclusion criteria were multicentric invasive growth pattern, unclear surgical margins, distant metastasis and a postoperative breast not suitable for interstitial brachytherapy. Primary endpoint was local tumour control. Morbidity, cosmetic outcome and QoL were assessed in 24/39 patients. Results The five year actuarial local control rate was 93% after a mean follow up of 57 (±30) months with two second local relapses. Overall survival and disease free survival, both at 5 years, were 87% and 77%, respectively. Late side effects Grade 1–2 were observed in 20/24 patients after a mean follow-up of 30 (±18) months. Late side effects ⩾Grade 3 occurred in 4/24 patients. Cosmetic outcome was excellent to fair in 76% of women. Overall QoL was comparable to a healthy control group. Mean scores of scales and items of QLQ-BR23 were comparable to primary breast conserving therapy. Conclusions Accelerated PDR-brachytherapy following breast conserving surgery (BCS) for local IBTR results in local tumour control comparable to mastectomy. Morbidity is moderate; the cosmetic outcome is good and hardly any impairment on QoL is observed.

The purpose of this study was to compare the peak pressure and peak force values obtained from two pressure assessment systems, the Dynamic Pedobarograph and the EMED SF. Twenty-one individuals with a mean age of 31.6 years walked barefoot over both systems using a two-step data collection protocol. Peak plantar pressures and peak vertical force values were measured under the heel, central forefoot, hallux, and entire foot for both systems. The results of this study demonstrated that the EMED SF system produced larger peak pressures under the central forefoot and hallux. The Pedobarograph, on the other hand, produced greater pressures under the heel and entire foot. With respect to peak vertical forces, the Pedobarograph showed significantly greater values under the heel and central forefoot compared with the EMED SF, but were significantly lower under the hallux and entire foot.