Untersuchungen von Surface Toughening auf die Verbindungsfestigkeit geklebter Proben unter reiner Mode-I und Mode-II Belastung

In dieser Arbeit wird der Einfluss von Surface Toughening auf Klebverbindungen unter reiner Mode I und Mode II Belastung untersucht. Ziel ist es neben dem Effekt auch die Energiefreisetzungsrate GIC und GIIC zu identifizieren. Dafür werden Double Cantilever Beam Proben und End Notched Flexure Proben verwendetet. Die Ergebnisse zeigen dabei auf, dass der Effekt des Surface Toughening zu einer deutlichen Erhöhung der Verbindungsfestigkeit führt. Unter Mode I (DCB-Versuch) muss das Kraftniveau deutlich ansteigen um die Klebverbindung zu zerstören und einen Riss weiterlaufen zu lassen. Unter Mode II wird der Riss gestoppt und bis zum Totalversagen der Probe weiter aufgehalten ohne sichtbare Beschädigung der restlichen Klebverbindung

Wer organisiert die "Entbehrlichen"? Viertelgestalterinnen und Viertelgestalter in benachteiligten Stadtquartieren

Auch wenn die Zivilgesellschaft in sozial benachteiligten Stadtvierteln häufig kaum sichtbar ist, gibt es wichtige Ausnahmen: Viertelgestalter_innen sind mit unermüdlicher Tatkraft bürgerschaftlich aktiv. Im Buch werden acht dieser außergewöhnlichen Menschen in ausführlichen Portraits vorgestellt. Wie kamen sie zu ihrer Rolle, welche Motive treiben sie in ihrem Engagement an, welche Wertvorstellungen vertreten sie? Die Studie ermöglicht detaillierte Einblicke in die Funktionsweise von Zivilgesellschaft in sozial schwachen Stadtteilen. Sie benennt Hindernisse und Schwierigkeiten für die Aktiven - zeigt aber auch Perspektiven, wie das partizipative Versprechen der modernen Bürgergesellschaft für sozial Benachteiligte eingelöst werden könnte.Civil engagement on the fringe of society - this volume shows what brings people in socially disadvantaged urban districts to engage in the civil society

Wer organisiert die "Entbehrlichen"?

Auch wenn die Zivilgesellschaft in sozial benachteiligten Stadtvierteln häufig kaum sichtbar ist, gibt es wichtige Ausnahmen: Viertelgestalter_innen sind mit unermüdlicher Tatkraft bürgerschaftlich aktiv. Im Buch werden acht dieser außergewöhnlichen Menschen in ausführlichen Portraits vorgestellt. Wie kamen sie zu ihrer Rolle, welche Motive treiben sie in ihrem Engagement an, welche Wertvorstellungen vertreten sie? Die Studie ermöglicht detaillierte Einblicke in die Funktionsweise von Zivilgesellschaft in sozial schwachen Stadtteilen. Sie benennt Hindernisse und Schwierigkeiten für die Aktiven - zeigt aber auch Perspektiven, wie das partizipative Versprechen der modernen Bürgergesellschaft für sozial Benachteiligte eingelöst werden könnte

Identification of DNA methylation changes at cis-regulatory elements during early steps of HSC differentiation using tagmentation-based whole genome bisulfite sequencing

Epigenetic alterations during cellular differentiation are a key molecular mechanism which both instructs and reinforces the process of lineage commitment. Within the haematopoietic system, progressive changes in the DNA methylome of haematopoietic stem cells (HSCs) are essential for the effective production of mature blood cells. Inhibition or loss of function of the cellular DNA methylation machinery has been shown to lead to a severe perturbation in blood production and is also an important driver of malignant transformation. HSCs constitute a very rare cell population in the bone marrow, capable of life-long self-renewal and multi-lineage differentiation. The low abundance of HSCs has been a major technological barrier to the global analysis of the CpG methylation status within both HSCs and their immediate progeny, the multipotent progenitors (MPPs). Within this Extra View article, we review the current understanding of how the DNA methylome regulates normal and malignant hematopoiesis. We also discuss the current methodologies that are available for interrogating the DNA methylation status of HSCs and MPPs and describe a new data set that was generated using tagmentation-based whole genome bisulfite sequencing (TWGBS) in order to comprehensively map methylated cytosines using the limited amount of genomic DNA that can be harvested from rare cell populations. Extended analysis of this data set clearly demonstrates the added value of genome-wide sequencing of methylated cytosines and identifies novel important cis-acting regulatory regions that are dynamically remodeled during the first steps of haematopoietic differentiation

Calcium-activated chloride current amplifies the response to urine in mouse vomeronasal sensory neurons

The vomeronasal organ (VNO) is an odor detection system that mediates many pheromone-sensitive behaviors. Vomeronasal sensory neurons (VSNs), located in the VNO, are the initial site of interaction with odors/pheromones. However, how an individual VSN transduces chemical signals into electrical signals is still unresolved. Here, we show that a Ca2+-activated Cl− current contributes ∼80% of the response to urine in mouse VSNs. Using perforated patch clamp recordings with gramicidin, which leaves intracellular chloride undisrupted, we found that the urine-induced inward current (Vhold = −80 mV) was decreased in the presence of chloride channel blockers. This was confirmed using whole cell recordings and altering extracellular chloride to shift the reversal potential. Further, the urine-induced currents were eliminated when both extracellular Ca2+ and Na+ were removed. Using inside-out patches from dendritic tips, we recorded Ca2+-activated Cl− channel activity. Several candidates for this Ca2+-activated Cl− channel were detected in VNO by reverse transcription–polymerase chain reaction. In addition, a chloride cotransporter, Na+-K+-2Cl− isoform 1, was detected and found to mediate much of the chloride accumulation in VSNs. Collectively, our data demonstrate that chloride acts as a major amplifier for signal transduction in mouse VSNs. This amplification would increase the responsiveness to pheromones or odorants

Identification of Regulatory Networks in HSCs and Their Immediate Progeny via Integrated Proteome, Transcriptome, and DNA Methylome Analysis

SummaryIn this study, we present integrated quantitative proteome, transcriptome, and methylome analyses of hematopoietic stem cells (HSCs) and four multipotent progenitor (MPP) populations. From the characterization of more than 6,000 proteins, 27,000 transcripts, and 15,000 differentially methylated regions (DMRs), we identified coordinated changes associated with early differentiation steps. DMRs show continuous gain or loss of methylation during differentiation, and the overall change in DNA methylation correlates inversely with gene expression at key loci. Our data reveal the differential expression landscape of 493 transcription factors and 682 lncRNAs and highlight specific expression clusters operating in HSCs. We also found an unexpectedly dynamic pattern of transcript isoform regulation, suggesting a critical regulatory role during HSC differentiation, and a cell cycle/DNA repair signature associated with multipotency in MPP2 cells. This study provides a comprehensive genome-wide resource for the functional exploration of molecular, cellular, and epigenetic regulation at the top of the hematopoietic hierarchy

Psychographische Verortung von Menschen mit Diabetes: Auswirkungen auf die Produktgestaltung und Kommunikation

Für den Erfolg eines Produktes oder einer Dienstleistung ist die umfassende Kenntnis der Bedürfnisse, Wahrnehmungs- und Entscheidungsfilter von Zielgruppen entscheidend. Nur eine zielgerichtete, zur Zielgruppe passende Produktentwicklung und -vermarktung kann Auf Dauer erfolgreich sein. Da soziodemographische Zielgruppendefinitionen heute alleine nicht valide genug sind, um Zielgruppen umfassend zu verstehen, werden im Marketing zu-nehmend psychographische Verortungen von Zielgruppen verwendet. Auch bei chronisch Kranken reichen rein soziodemographische und medizinische Kriterien nicht aus, um Produkte und Dienstleistungen passend zu gestalten. Psychographische Erkenntnisse können die klassischen Kriterien sinnvoll ergänzen. Am Beispiel von Menschen mit Diabetes wird in einer internationalen empirischen Studie gezeigt, dass sich Menschen mit Diabetes mit Hilfe eines neuropsychologisch fundierten, visuellen Testverfahrens (dem u.a. an der NORD-AKADEMIE entwickelten Visual Questionnaire, ViQ) eindeutig psychographisch verorten lassen. Die Implikationen und Anwendungsmöglichkeiten dieser psychographischen Erkenntnisse für die Produktentwicklung, Kommunikation, Vertrieb und Marketing bei Krankenkassen, medizinischem Personal und der Pharmabranche werden aufgezeigt und kritisch diskutiert. --

Limits of Calcium Clearance by Plasma Membrane Calcium ATPase in Olfactory Cilia

BACKGROUND: In any fine sensory organelle, a small influx of Ca(2+) can quickly elevate cytoplasmic Ca(2+). Mechanisms must exist to clear the ciliary Ca(2+) before it reaches toxic levels. One such organelle has been well studied: the vertebrate olfactory cilium. Recent studies have suggested that clearance from the olfactory cilium is mediated in part by plasma membrane Ca(2+)-ATPase (PMCA). PRINCIPAL FINDINGS: In the present study, electrophysiological assays were devised to monitor cytoplasmic free Ca(2+) in single frog olfactory cilia. Ca(2+) was allowed to enter isolated cilia, either through the detached end or through membrane channels. Intraciliary Ca(2+) was monitored via the activity of ciliary Ca(2+)-gated Cl(-) channels, which are sensitive to free Ca(2+) from about 2 to 10 microM. No significant effect of MgATP on intraciliary free Ca(2+) could be found. Carboxyeosin, which has been used to inhibit PMCA, was found to substantially increase a ciliary transduction current activated by cyclic AMP. This increase was ATP-independent. CONCLUSIONS: Alternative explanations are suggested for two previous experiments taken to support a role for PMCA in ciliary Ca(2+) clearance. It is concluded that PMCA in the cilium plays a very limited role in clearing the micromolar levels of intraciliary Ca(2+) produced during the odor response

Olfactory response termination involves Ca2+-ATPase in vertebrate olfactory receptor neuron cilia

In vertebrate olfactory receptor neurons (ORNs), odorant-induced activation of the transduction cascade culminates in production of cyclic AMP, which opens cyclic nucleotide–gated channels in the ciliary membrane enabling Ca2+ influx. The ensuing elevation of the intraciliary Ca2+ concentration opens Ca2+-activated Cl− channels, which mediate an excitatory Cl− efflux from the cilia. In order for the response to terminate, the Cl− channel must close, which requires that the intraciliary Ca2+ concentration return to basal levels. Hitherto, the extrusion of Ca2+ from the cilia has been thought to depend principally on a Na+–Ca2+ exchanger

Assessment of the olfactory function in Italian patients with type 3 von Willebrand disease caused by a homozygous 253 Kb deletion involving VWF and TMEM16B/ANO2.

Type 3 Von Willebrand disease is an autosomal recessive disease caused by the virtual absence of the von Willebrand factor (VWF). A rare 253 kb gene deletion on chromosome 12, identified only in Italian and German families, involves both the VWF gene and the N-terminus of the neighbouring TMEM16B/ANO2 gene, a member of the family named transmembrane 16 (TMEM16) or anoctamin (ANO). TMEM16B is a calcium-activated chloride channel expressed in the olfactory epithelium. As a patient homozygous for the 253 kb deletion has been reported to have an olfactory impairment possibly related to the partial deletion of TMEM16B, we assessed the olfactory function in other patients using the University of Pennsylvania Smell Identification Test (UPSIT). The average UPSIT score of 4 homozygous patients was significantly lower than that of 5 healthy subjects with similar sex, age and education. However, 4 other members of the same family, 3 heterozygous for the deletion and 1 wild type, had a slightly reduced olfactory function indicating that socio-cultural or other factors were likely to be responsible for the observed difference. These results show that the ability to identify odorants of the homozygous patients for the deletion was not significantly different from that of the other members of the family, showing that the 253 kb deletion does not affect the olfactory performance. As other genes may compensate for the lack of TMEM16B, we identified some predicted functional partners from in silico studies of the protein-protein network of TMEM16B. Calculation of diversity for the corresponding genes for individuals of the 1000 Genomes Project showed that TMEM16B has the highest level of diversity among all genes of the network, indicating that TMEM16B may not be under purifying selection and suggesting that other genes in the network could compensate for its function for olfactory ability