Berücksichtigung statistischer Oberflächenkenngrößen bei der numerischen Simulation hydrodynamisch wirkender Radialgleitlager im Mischreibungsbereich

Gegenstand der vorliegenden wissenschaftlichen Arbeit war die Untersuchung, ob eine Beschreibung der Druckkomponenten im Mischreibungsbereich eines hydrodynamisch wirkenden Radialgleitlagers durch die Berücksichtigung experimentell ermittelter statistischer Oberflächenkenngrößen möglich ist. Weiterhin wurde geprüft, welche flächenhaft bestimmten Kenngrößen für die Oberflächendefinition in der Simulation geeignet sind. Ausgehend von dem Modellansatz der Lastaufteilung im Bereich der Mischreibung wurden zwei separate Modelle für die jeweiligen Druckkomponenten erstellt

Evaluation des Bundesprogramms Ökologischer Landbau

Parallel zu seiner Umsetzung wurde das Bundesprogramm Ökologischer Landbau (BÖL) ab 2003 begleitend evaluiert. Die Evaluierung des Gesamtprogramms führte die "Gesellschaft für Innovationsforschung und Beratung mbH Berlin (GIB)" durch. Die Evaluierung des Maßnahmenbereiches C2 ("Information der Verbraucher über das Produktionssystem ökologischer Landbau") erfolgte separat durch "Partizip und Dr. Brombacher & Weber". Deren Ergebnisse sind in den nun vorliegenden Abschlussbericht eingeflossen. Die an die GIB vergebene Gesamtevaluierung hatte den Auftrag, die Umsetzung des Programms kritisch zu begleiten und möglichst schnell Ergebnisse zur Ziel(gruppen)erreichung, Wirksamkeit und Effizienz der Einzelmaßnahmen zu liefern. Ziel war es, noch im laufenden Programm und für Planungsarbeiten im Falle seiner Verlängerung Empfehlungen zur Optimierung einzelner Bereiche bzw. zur Korrektur von Fehlentwicklungen auszusprechen. Gegenstand der Evaluation waren alle realisierten Maßnahmen in den Bereichen A - C (Landwirtschaftliche Produktion; Erfassung und Verarbeitung; Handel, Vermarktung und Verbraucher). Weiterhin wurde der Komplex D - E (Forschung und Entwicklung, Technologie- und Wissenstransfer) evaluiert. Forschungsergebnisse konnten im Rahmen der Evaluation noch nicht bewertet werden, da ein Großteil der Projekte erst Ende 2003 / Anfang 2004 auslief, noch nicht ausgewertet war oder aufgrund der zwischenzeitlichen Entscheidung zur Fortsetzung des BÖL teilweise verlängert wurde. Daher konzentrierte sich die GIB auf die Bewertung des Prozessmanagements. Schließlich stand die Umsetzung und Betreuung des Bundesprogramms durch die Geschäftsstelle Bundesprogramm Ökologischer Landbau (GS-BÖL) in der BLE auf dem Prüfstand. Im Rahmen der Evaluierung fand Anfang Dezember 2003 ein Reflexionsworkshop statt, an dem maßgeblich am Bundesprogramm beteiligte bzw. im Ökosektor engagierte Akteure, Vertreter der Politik, der Geschäftsstelle, der Wissenschaft usw. teilnahmen. Ziel war die Präsentation und erste Diskussion der Evaluierungsergebnisse in diesem Forum, um daraus u.a. Schlussfolgerungen für die Fortsetzung des BÖL ab 2004 ff. ableiten zu können. Dieser Eintrag in der Datenbank Organic Eprints enthält den ausführlichen Endbericht der Evaluierung, den Anhang mit Befragungsergebnissen, Graphiken und Auswertungen zu den bewerteten Einzelmaßnahmen und Prozessen sowie das Protokoll des Reflexionsworkshops. Die Geschäftsstelle Bundesprogramm Ökologischer Landbau bittet um Anmerkungen, Anregungen und Kritik zum Evaluierungsbericht (E-Mail: [email protected], Betreff: Feedback zur Evaluation des BÖL)

Minderung von Treibhausgas-Emissionen der Landwirtschaft

In dem Bericht werden der Treibhausgas (THG)-Ausstoß der sächsischen Landwirtschaft, die bisher erbrachten Klimaschutzleistungen und die Minderungspotenziale bis zum Jahr 2020 dargestellt. Für den gewählten Bilanzkreis hat die sächsische Landwirtschaft ca. 7,6 % zum THG-Ausstoß in Sachsen beigetragen. Im Vergleich zum Jahr 2000 konnte der THG-Ausstoß um ca. 5 % vermindert werden. Bis zum Jahr 2020 könnte ein THG-Minderungspotenzial von weiteren etwa 5 % erschlossen werden. Die Veröffentlichung richtet sich vorrangig an Fachleute aus der Landwirtschaft, aber auch an die Verbraucher, die ebenfalls einen Beitrag zur Minderung des THG-Ausstoßes leisten können

The Actin Targeting Compound Chondramide Inhibits Breast Cancer Metastasis via Reduction of Cellular Contractility

Background: A major player in the process of metastasis is the actin cytoskeleton as it forms key structures in both invasion mechanisms, mesenchymal and amoeboid migration. We tested the actin binding compound Chondramide as potential anti-metastatic agent. Methods: In vivo, the effect of Chondramide on metastasis was tested employing a 4T1-Luc BALB/c mouse model. In vitro, Chondramide was tested using the highly invasive cancer cell line MDA-MB-231 in Boyden-chamber assays, fluorescent stainings, Western blot and Pull down assays. Finally, the contractility of MDA-MB-231 cells was monitored in 3D environment and analyzed via PIV analysis. Results: In vivo, Chondramide treatment inhibits metastasis to the lung and the migration and invasion of MDA-MB-231 cells is reduced by Chondramide in vitro. On the signaling level, RhoA activity is decreased by Chondramide accompanied by reduced MLC-2 and the stretch induced guanine nucleotide exchange factor Vav2 activation. At same conditions, EGF-receptor autophosphorylation, Akt and Erk as well as Rac1 are not affected. Finally, Chondramide treatment disrupted the actin cytoskeleton and decreased the ability of cells for contraction. Conclusions: Chondramide inhibits cellular contractility and thus represents a potential inhibitor of tumor cell invasion

An Inverse Thermogelling Bioink Based on an ABA-Type Poly(2-oxazoline) Amphiphile

Hydrogels are key components in several biomedical research areas such as drug delivery, tissue engineering, and biofabrication. Here, a novel ABA-type triblock copolymer comprising poly(2-methyl-2-oxazoline) as the hydrophilic A blocks and poly(2-phenethyl-2-oxazoline) as the aromatic and hydrophobic B block is introduced. Above the critical micelle concentration, the polymer self-assembles into small spherical polymer micelles with a hydrodynamic radius of approx 8-8.5 nm. Interestingly, this specific combination of hydrophilic and hydrophobic aromatic moieties leads to rapid thermoresponsive inverse gelation at polymer concentrations above a critical gelation concentration (20 wt %) into a macroporous hydrogel of densely packed micelles. This hydrogel exhibited pronounced viscoelastic solid-like properties, as well as extensive shear-thinning, rapid structure recovery, and good strain resistance properties. Excellent 3D-printability of the hydrogel at lower temperature opens a wide range of different applications, for example, in the field of biofabrication. In preliminary bioprinting experiments using NIH 3T3 cells, excellent cell viabilities of more than 95% were achieved. The particularly interesting feature of this novel material is that it can be used as a printing support in hybrid bioink systems and sacrificial bioink due to rapid dissolution at physiological conditions.Peer reviewe

Epigenetic Control of the foxp3 Locus in Regulatory T Cells

Compelling evidence suggests that the transcription factor Foxp3 acts as a master switch governing the development and function of CD4(+) regulatory T cells (Tregs). However, whether transcriptional control of Foxp3 expression itself contributes to the development of a stable Treg lineage has thus far not been investigated. We here identified an evolutionarily conserved region within the foxp3 locus upstream of exon-1 possessing transcriptional activity. Bisulphite sequencing and chromatin immunoprecipitation revealed complete demethylation of CpG motifs as well as histone modifications within the conserved region in ex vivo isolated Foxp3(+)CD25(+)CD4(+) Tregs, but not in naïve CD25(−)CD4(+) T cells. Partial DNA demethylation is already found within developing Foxp3(+) thymocytes; however, Tregs induced by TGF-β in vitro display only incomplete demethylation despite high Foxp3 expression. In contrast to natural Tregs, these TGF-β–induced Foxp3(+) Tregs lose both Foxp3 expression and suppressive activity upon restimulation in the absence of TGF-β. Our data suggest that expression of Foxp3 must be stabilized by epigenetic modification to allow the development of a permanent suppressor cell lineage, a finding of significant importance for therapeutic applications involving induction or transfer of Tregs and for the understanding of long-term cell lineage decisions

Lenalidomide/melphalan/dexamethasone in newly diagnosed patients with immunoglobulin light chain amyloidosis: results of a prospective phase 2 study with long-term follow up

Chemotherapy in light chain amyloidosis aims to normalize the involved free light chain in serum, which leads to an improvement, or at least stabilization of organ function in most responding patients. We performed a prospective single center phase 2 trial with 50 untreated patients not eligible for high-dose treatment. The treatment schedule comprised 6 cycles of oral lenalidomide, melphalan and dexamethasone every 4 weeks. After 6 months, complete remission was achieved in 9 patients (18%), very good partial remission in 16 (32%) and partial response in 9 (18%). Overall, organ response was observed in 24 patients (48%). Hematologic and cardiac toxicities were predominant adverse events. Mortality at 3 months was low at 4% (n=2) despite the inclusion of 36% of patients (n=18) with cardiac stage Mayo 3. After a median follow-up of 50 months, median overall and event-free survival were 67.5 months and 25.1 months, respectively. We conclude that the treatment of lenalidomide, melphalan and dexamethasone is very effective in achieving a hematologic remission, organ response and, consecutively, a long survival in transplant ineligible patients with light chain amyloidosis. However, as toxicity and tolerability are the major problems of a 3-drug regimen, a strict surveillance program is necessary and sufficient to avoid severe toxicities. clinicaltrials.gov Identifier: 00883623 (Eudract2008-001405-41)

Methylation matters: binding of Ets-1 to the demethylated Foxp3 gene contributes to the stabilization of Foxp3 expression in regulatory T cells

The forkhead-box protein P3 (Foxp3) is a key transcription factor for the development and suppressive activity of regulatory T cells (Tregs), a T cell subset critically involved in the maintenance of self-tolerance and prevention of over-shooting immune responses. However, the transcriptional regulation of Foxp3 expression remains incompletely understood. We have previously shown that epigenetic modifications in the CpG-rich Treg-specific demethylated region (TSDR) in the Foxp3 locus are associated with stable Foxp3 expression. We now demonstrate that the methylation state of the CpG motifs within the TSDR controls its transcriptional activity rather than a Treg-specific transcription factor network. By systematically mutating every CpG motif within the TSDR, we could identify four CpG motifs, which are critically determining the transcriptional activity of the TSDR and which serve as binding sites for essential transcription factors, such as CREB/ATF and NF-κB, which have previously been shown to bind to this element. The transcription factor Ets-1 was here identified as an additional molecular player that specifically binds to the TSDR in a demethylation-dependent manner in vitro. Disruption of the Ets-1 binding sites within the TSDR drastically reduced its transcriptional enhancer activity. In addition, we found Ets-1 bound to the demethylated TSDR in ex vivo isolated Tregs, but not to the methylated TSDR in conventional CD4+ T cells. We therefore propose that Ets-1 is part of a larger protein complex, which binds to the TSDR only in its demethylated state, thereby restricting stable Foxp3 expression to the Treg lineage

Finding Our Way through Phenotypes

Despite a large and multifaceted effort to understand the vast landscape of phenotypic data, their current form inhibits productive data analysis. The lack of a community-wide, consensus-based, human- and machine-interpretable language for describing phenotypes and their genomic and environmental contexts is perhaps the most pressing scientific bottleneck to integration across many key fields in biology, including genomics, systems biology, development, medicine, evolution, ecology, and systematics. Here we survey the current phenomics landscape, including data resources and handling, and the progress that has been made to accurately capture relevant data descriptions for phenotypes. We present an example of the kind of integration across domains that computable phenotypes would enable, and we call upon the broader biology community, publishers, and relevant funding agencies to support efforts to surmount today's data barriers and facilitate analytical reproducibility