Impact of degeneration and material pairings on cartilage friction: Cartilage versus glass

The association of knee joint osteoarthritis and altered frictional properties of the degenerated cartilage remains ambiguous, because previous in vitro studies did not consider the characteristic loads and velocities during gait. Therefore, the aim of this study was to quantify the friction behavior of degenerated human cartilage under characteristic stance and swing phase conditions. A dynamic pin-on-plate tribometer was used to test the tribological systems of cartilage against cartilage and cartilage against glass, both with synthetic synovial fluid as lubricant. Using the International Cartilage Repair Society classification, the cartilage samples were assigned to a mildly or a severely degenerated group before testing. Friction coefficients were calculated under stance and swing phase conditions at the beginning of the test and after 600 s of testing. The most important finding of this study is that cartilage against glass couplings displayed significantly higher friction for the severely degenerated samples compared to the mildly degenerated ones, whereas cartilage against cartilage couplings only indicated slight tendencies under the observed test conditions. Consequently, care should be taken when transferring in vitro findings from cartilage against cartilage couplings to predict the friction behavior in vivo. Therefore, we recommend in vitro tribological testing methods which account for gait-like loading conditions and to replicate physiological material pairings, particularly in preclinical medical device validation studies

Improving the Detection Limit in a Capillary Raman System for In Situ Gas Analysis by Means of Fluorescence Reduction

Raman spectroscopy for low-pressure or trace gas analysis is rather challenging, in particular in process control applications requiring trace detection and real-time response; in general, enhancement techniques are required. One possible enhancement approach which enjoys increasing popularity makes use of an internally-reflective capillary as the gas cell. However, in the majority of cases, such capillary systems were often limited in their achievable sensitivity by a significant fluorescence background, which is generated as a consequence of interactions between the laser light and optical glass components in the setup. In order to understand and counteract these problems we have investigated a range of fluorescence-reducing measures, including the rearrangement of optical elements, and the replacement of glass components--including the capillary itself--by metal alternatives. These studies now have led to a capillary setup in which fluorescence is practically eliminated and substantial signal enhancement over standard Raman setups is achieved. With this improved (prototype) setup, detection limits of well below 1 mbar could be obtained in sub-second acquisition times, demonstrating the potential of capillary Raman spectroscopy for real-time, in situ gas sensing and process control applications, down to trace level concentrations

Creation of multiple nanodots by single ions

In the challenging search for tools that are able to modify surfaces on the nanometer scale, heavy ions with energies of several 10 MeV are becoming more and more attractive. In contrast to slow ions where nuclear stopping is important and the energy is dissipated into a large volume in the crystal, in the high energy regime the stopping is due to electronic excitations only. Because of the extremely local (< 1 nm) energy deposition with densities of up to 10E19 W/cm^2, nanoscaled hillocks can be created under normal incidence. Usually, each nanodot is due to the impact of a single ion and the dots are randomly distributed. We demonstrate that multiple periodically spaced dots separated by a few 10 nanometers can be created by a single ion if the sample is irradiated under grazing angles of incidence. By varying this angle the number of dots can be controlled.Comment: 12 pages, 6 figure

Magnetic-Responsive Carbon Nanotubes Composite Scaffolds for Chondrogenic Tissue Engineering

The demand for engineered scaffolds capable of delivering multiple cues to cells continues to grow as the interplay between cell fate with microenvironmental and external cues is revealed. Emphasis has been given to develop stimuli-responsive scaffolds. These scaffolds are designed to sense an external stimulus triggering a specific response (e.g., change in the microenvironment, release therapeutics, etc.) and then initiate/modulate a desired biofunction. Here, magnetic-responsive carboxylated multi-walled carbon nanotubes (cMWCNTs) are integrated into 3D collagen/polylactic acid (PLA) scaffold via a reproducible filtration-based method. The integrity and biomechanical performance of the collagen/PLA scaffolds are preserved after cMWCNT integration. In vitro safety assessment of cMWCNT/collagen/PLA scaffolds shows neither cytotoxicity effects nor macrophage pro-inflammatory response, supporting further in vitro studies. The cMWCNT/collagen/PLA scaffolds enhance chondrocytes metabolic activity while maintaining high cell viability and extracellular matrix (i.e., type II collagen and aggrecan) production. Comprehensive in vitro study applying static and pulsed magnetic field on seeded scaffolds shows no specific cell response in dependence with the applied field. This result is independent of the presence or absence of cMWCNT into the collagen/PLA scaffolds. Taken together, these findings provide additional evidence of the benefits to exploit the CNTs outstanding properties in the design of stimuli-responsive scaffolds.publishedVersio

Phase I/II intra-patient dose escalation study of vorinostat in children with relapsed solid tumor, lymphoma, or leukemia

Background: Until today, adult and pediatric clinical trials investigating single-agent or combinatorial HDAC inhibitors including vorinostat in solid tumors have largely failed to demonstrate efficacy. These results may in part be explained by data from preclinical models showing significant activity only at higher concentrations compared to those achieved with current dosing regimens. In the current pediatric trial, we applied an intra-patient dose escalation design. The purpose of this trial was to determine a safe dose recommendation (SDR) of single-agent vorinostat for intra-patient dose escalation, pharmacokinetic analyses (PK), and activity evaluation in children (3-18 years) with relapsed or therapy-refractory malignancies. Results: A phase I intra-patient dose (de)escalation was performed until individual maximum tolerated dose (MTD). The starting dose was 180 mg/m(2)/day with weekly dose escalations of 50 mg/m(2) until DLT/maximum dose. After MTD determination, patients seamlessly continued in phase II with disease assessments every 3 months. PK and plasma cytokine profiles were determined. Fifty of 52 patients received treatment. n = 27/50 (54%) completed the intra-patient (de)escalation and entered phase II. An SDR of 130 mg/m(2)/day was determined (maximum, 580 mg/m(2)/day). n = 46/50 (92%) patients experienced treatment-related AEs which were mostly reversible and included thrombocytopenia, fatigue, nausea, diarrhea, anemia, and vomiting. n = 6/50 (12%) had treatment-related SAEs. No treatment-related deaths occurred. Higher dose levels resulted in higher C-max. Five patients achieved prolonged disease control (> 12 months) and showed a higher C-max (> 270 ng/mL) and MTDs. Best overall response (combining PR and SD, no CR observed) rate in phase II was 6/27 (22%) with a median PFS and OS of 5.3 and 22.4 months. Low levels of baseline cytokine expression were significantly correlated with favorable outcome. Conclusion: An SDR of 130 mg/m(2)/day for individual dose escalation was determined. Higher drug exposure was associated with responses and long-term disease stabilization with manageable toxicity. Patients with low expression of plasma cytokine levels at baseline were able to tolerate higher doses of vorinostat and benefited from treatment. Baseline cytokine profile is a promising potential predictive biomarker

Newly defined ATP-binding cassette subfamily B member 5 positive dermal mesenchymal stem cells promote healing of chronic iron-overload wounds via secretion of interleukin-1 receptor antagonist

In this study, we report the beneficial effects of a newly identified dermal cell subpopulation expressing the ATP‐binding cassette subfamily B member 5 (ABCB5) for the therapy of nonhealing wounds. Local administration of dermal ABCB5+‐derived mesenchymal stem cells (MSCs) attenuated macrophage‐dominated inflammation and thereby accelerated healing of full‐thickness excisional wounds in the iron‐overload mouse model mimicking the nonhealing state of human venous leg ulcers. The observed beneficial effects were due to interleukin‐1 receptor antagonist (IL‐1RA) secreted by ABCB5+‐derived MSCs, which dampened inflammation and shifted the prevalence of unrestrained proinflammatory M1 macrophages toward repair promoting anti‐inflammatory M2 macrophages at the wound site. The beneficial anti‐inflammatory effect of IL‐1RA released from ABCB5+‐derived MSCs on human wound macrophages was conserved in humanized NOD‐scid IL2rγ null mice. In conclusion, human dermal ABCB5+ cells represent a novel, easily accessible, and marker‐enriched source of MSCs, which holds substantial promise to successfully treat chronic nonhealing wounds in humans

Search for supersymmetry in events with b-quark jets and missing transverse energy in pp collisions at 7 TeV

Results are presented from a search for physics beyond the standard model based on events with large missing transverse energy, at least three jets, and at least one, two, or three b-quark jets. The study is performed using a sample of proton-proton collision data collected at sqrt(s) = 7 TeV with the CMS detector at the LHC in 2011. The integrated luminosity of the sample is 4.98 inverse femtobarns. The observed number of events is found to be consistent with the standard model expectation, which is evaluated using control samples in the data. The results are used to constrain cross sections for the production of supersymmetric particles decaying to b-quark-enriched final states in the context of simplified model spectra.Comment: Submitted to Physical Review

Risk governance in organizations

Dieses Buch dokumentiert 10 Jahre Risk-Governance-Forschung an der Universität Siegen. In 50 Beiträgen reflektieren Forscher und Praktiker Risk Governance vor dem Hintergrund ihrer eigenen Forschungen und/oder Erfahrungen und geben jeweils einen Entwicklungsimpuls für die Zukunft der Risk Governance. Das Buch zeigt die große Bandbreite und Tiefe des Forschungsgebietes auf und diskutiert Grundannahmen, Implementierungsfragen, die Rolle der Risk Governance als Transformationsmotor, ihre Wirkung in den verschiedenen betrieblichen Funktionen, Entwicklungsperspektiven und den Beitrag der Risk Governance zu einer nachhaltigen Ausrichtung von Unternehmen.This book documents 10 years of risk governance research at the University of Siegen. In 50 contributions, researchers and practitioners reflect on risk governance against the background of their own research and/or experience and provide a development impetus for the future of risk governance. The book shows the wide range and depth of the research field and discusses basic assumptions, implementation issues, the role of risk governance as transformation engine, its impact in the various operational functions, development perspectives, and the contribution of risk governance to a sustainable orientation of companies