Spinmarkierte Oligopeptide als substratanaloge Inhibitoren der Leucinaminopeptidase

Spin Labeled Oligopeptides as Substrate Analogous Inhibitors of Leucine Aminopeptidase The synthesis of L-Thr(Bu^t)-(L-Phe)_n-SL peptides C-terminal labeled with the nitroxide spin label 2,2,5,5-tetramethyl-3-amino-pyrrolidin-1-oxyl, is described and e.s.r. parameters of the labeled compounds are presented. As shown by e.s.r. spectroscopy studies Thr(Bu^t)-Phe-SL is a competitive inhibitor of the leucine aminopeptidase and is bound by the enzyme with high affinity.     

The influence of temperament style on a student’s choice of and performance in a computer programming course

This study is an attempt to determine whether it is necessary to include temperament style when compiling an instrument to predict a student’s chances of success in a computer programming course. Temperament style is seen as the combination of qualities which constitute the natural disposition of an individual and which affect actions, thinking and emotions. The DISC model, as adapted by Boyd [Boyd, C. F. (1994). Different children, different needs: the art of adjustable parenting. Oregon: Questar Publishers Inc.], views people as behaving along two orthogonal dimensions: the speed at which a person moves through life, and his/her general focus when doing things, i.e. on people or on tasks. This study proved that both of these dimensions have an influence on the performance of students in a computer programming course while one of them also has an influence on a student’s choice to pursue a programming course.     

Nanogel Encapsulated Hydrogels As Advanced Wound Dressings for the Controlled Delivery of Antibiotics

Biocompatible and degradable dual-delivery gel systems based on hyperbranched dendritic−linear−dendritic copolymers (HBDLDs) is herein conceptualized and accomplished via thiol-ene click chemistry. The elasticity of the hydrogels is tunable by varying the lengths of PEG (2, 6, 10 kDa) or the dry weight percentages (20, 30, 40 wt%), and are found to range from 2–14.7 kPa, comparable to human skin. The co-delivery of antibiotics is achieved, where the hydrophilic drug novobiocin sodium salt (NB) is entrapped within the hydrophilic hydrogel, while the hydrophobic antibiotic ciprofloxacin (CIP) is encapsulated within the dendritic nanogels (DNGs) with hydrophobic cores (DNGs-CIP). The DNGs-CIP with drug loading capacity of 2.83 wt% are then physically entrapped within the hybrid hydrogels through UV curing. The hybrid hydrogels enable the quick release of NB and prolonged released of CIP. In vitro cell infection assays showed that the antibiotic-loaded hybrid hydrogels are able to treat bacterial infections with significant bacterial reduction. Hybrid hydrogel band aids are fabricated and exhibited better antibacterial activity compared with commercial antimicrobial band aids. Remarkably, most hydrogels and hybrid hydrogels show enhanced human dermal cell proliferation and could be degraded into non-toxic constituents, showing great promise as wound dressing materials.     

In Vivo Performance and Structural Relaxation of Biodegradable Bone Implants Made from Mg?Zn?Ca Bulk Metallic Glasses

A study of Mg‐based bulk metallic glasses (BMGs) as biodegradable bone implants is presented. The implantation site can affect performance, so the BMGs were evaluated in vivo in rat femurs using µ‐CT scans at various times for more than 90 days. Estimates of H₂ evolution correlate well with previous in vitro studies and bone–implant contact is similar to that for Ti pins. One potential drawback of Mg‐based BMGs in this application is embrittlement due to structural relaxation. Here, relaxation at 20 and 37 °C is examined, and an increase in the characteristic relaxation time, from 10 to 30 days at 20 °C, is observed as Zn increases from 29 to 32 at.%, correlating with dramatically reduced hydrogen evolution.     

The calculations of dispersion coefficients inside two‐dimensional randomly packed beds of circular particles

The longitudinal (D_L) and transverse (D_T) dispersion coefficients in two‐dimensional (2‐D) randomly packed beds of circular particles in a laminar flow regime are derived. A 2‐D discrete system of particles is divided into cells using modified Voronoi diagrams. The relationship between the variation of the stream function and the averaged vorticity is obtained from computational fluid dynamics (CFD) simulations. The whole flow pattern is then obtained by using the principle of energy dissipation rate minimization. The obtained values of D_L agree well with 3‐D experimental data for all velocities investigated. At very high velocities, D_T in 2‐D appears to be higher than 3‐D experimental data. In addition, the effects of particle‐size distributions, packing structure, and porosity on the D_L and D_T were studied. One result was that an increase in the width of the particle‐size distribution resulted in higher values of D_L and D_T at high velocities. © 2012 American Institute of Chemical Engineers AIChE J, 59: 1002–1011, 2013     

A Human Osteochondral Tissue Model Mimicking Cytokine-Induced Key Features of Arthritis In Vitro

Adequate tissue engineered models are required to further understand the (patho)physiological mechanism involved in the destructive processes of cartilage and subchondral bone during rheumatoid arthritis (RA). Therefore, we developed a human in vitro 3D osteochondral tissue model (OTM), mimicking cytokine-induced cellular and matrix-related changes leading to cartilage degradation and bone destruction in order to ultimately provide a preclinical drug screening tool. To this end, the OTM was engineered by co-cultivation of mesenchymal stromal cell (MSC)-derived bone and cartilage components in a 3D environment. It was comprehensively characterized on cell, protein, and mRNA level. Stimulating the OTM with pro-inflammatory cytokines, relevant in RA (tumor necrosis factor α, interleukin-6, macrophage migration inhibitory factor), caused cell- and matrix-related changes, resulting in a significantly induced gene expression of lactate dehydrogenase A, interleukin-8 and tumor necrosis factor α in both, cartilage and bone, while the matrix metalloproteases 1 and 3 were only induced in cartilage. Finally, application of target-specific drugs prevented the induction of inflammation and matrix-degradation. Thus, we here provide evidence that our human in vitro 3D OTM mimics cytokine-induced cell- and matrix-related changes—key features of RA—and may serve as a preclinical tool for the evaluation of both new targets and potential drugs in a more translational setup.     

Biomarkers of Chondrocyte Apoptosis and Autophagy in Osteoarthritis

Cell death with morphological and molecular features of apoptosis has been detected in osteoarthritic (OA) cartilage, which suggests a key role for chondrocyte death/survival in the pathogenesis of OA. Identification of biomarkers of chondrocyte apoptosis may facilitate the development of novel therapies that may eliminate the cause or, at least, slow down the degenerative processes in OA. The aim of this review was to explore the molecular markers and signals that induce chondrocyte apoptosis in OA. A literature search was conducted in PubMed, Scopus, Web of Science and Google Scholar using the keywords chondrocyte death, apoptosis, osteoarthritis, autophagy and biomarker. Several molecules considered to be markers of chondrocyte apoptosis will be discussed in this brief review. Molecular markers and signalling pathways associated with chondroycte apoptosis may turn out to be therapeutic targets in OA and approaches aimed at neutralizing apoptosis-inducing molecules may at least delay the progression of cartilage degeneration in OA.     

Natural Freezing, Drying, and Composting for Treatment of Septic Sludge

A full-scale experimental plant intended for local treatment of septic sludge, situated in northern Sweden, is presented in this paper. The concept investigated included natural freezing, thawing, and drying in combination with composting. The experimental plant consisted of an undrained freezing-thawing-drying bed and a heat-insulated composter. About 500 L of fresh sludge, with a dry matter (DM) content of 4–5%, collected from a septic tank employed by one family, was transferred to the freezing-thawing-drying bed in the beginning of November 1996. During the winter months, the sludge froze and then thawed in the middle of May 1997. During a drying period of three weeks, the DM content increased from 10.6–21.3 to 25–95%. The final sludge volume and weight were 180 L and 54 kg, respectively. Approximate concentrations of nitrogen, phosphorus and total organic carbon of the dried sludge were determined to be 23, 5.9, and 346 g∕kg DM. From June until the end of August, the sludge was cocomposted with kitchen refuse. Within two weeks, the composting temperature exceeded 65°C. The measured composting temperature indicated a high pathogen die-off, but before this concept can be suggested as an alternative to conventional septic sludge treatment, further studies should be conducted, including direct measurements of pathogens. The concept, however, has proved to be of interest in cold regions due to its simple construction and operation.