Co-Oxidative Transformation of Piperine to Piperonal and 3,4-Methylenedioxycinnamaldehyde by a Lipoxygenase from Pleurotus sapidus

The valuable aroma compound piperonal with its vanilla-like olfactory properties is of high interest for the fragrance and flavor industry. A lipoxygenase (LOX_Psa1) of the basidiomycete Pleurotus sapidus was identified to convert piperine, the abundant pungent principle of black pepper (Piper nigrum), to piperonal and a second volatile product, 3,4-methylenedioxycinnamaldehyde, with a vanilla-like odor through an alkene cleavage. The reaction principle was co-oxidation, as proven by its dependence on the presence of linoleic or α-linolenic acid, common substrates of lipoxygenases. Optimization of the reaction conditions (substrate concentrations, reaction temperature and time) led to a 24-fold and 15-fold increase of the piperonal and 3,4-methylenedioxycinnamaldehyde concentration using the recombinant enzyme. Monokaryotic strains showed different concentrations of and ratios between the two reaction products.     

Enhanced π-π interactions between a C60 fullerene and a buckle bend on a double-walled carbon nanotube

In situ low-voltage aberration corrected transmission electron microscopy (TEM) observations of the dynamic entrapment of a C₆₀ molecule in the saddle of a bent double-walled carbon nanotube is presented. The fullerene interaction is non-covalent, suggesting that enhanced π-π interactions (van der Waals forces) are responsible. Classical molecular dynamics calculations confirm that the increased interaction area associated with a buckle is sufficient to trap a fullerene. Moreover, they show hopping behavior in agreement with our experimental observations. Our findings further our understanding of carbon nanostructure interactions, which are important in the rapidly developing field of low-voltage aberration corrected TEM and nano-carbon device fabrication.      

Robust production planning and control for multi-stage systems with flexible final assembly lines

Production planning of final assembly systems is a challenging task, as the often fluctuating order volumes require flexible solutions. Besides, the calculated plans need to be robust against the process-level disturbances and stochastic nature of some parameters like manual processing times or machine availability. In the paper, a simulation-based optimisation method is proposed that utilises lower level shop floor data to calculate robust production plans for final assembly lines of a flexible, multi-stage production system. In order to minimise the idle times when executing the plans, the capacity control that specifies the proper operator–task assignments is also determined. The analysed multi-stage system is operated with a pull strategy, which means that the production at the final assembly lines generates demands for the preceding stages providing the assembled components. In order to guarantee the feasibility of the plans calculated for the final assembly lines, a decomposition approach is proposed to optimise the production plan of preceding stages. By this way, the robust production can be ensured resulting in reduced losses and overall production costs even though the system is exposed to changes and disturbances.     

Making Epothilones Fluoresce: Design,Synthesis, and Biological Characterization of a Fluorescent N12‐Aza‐Epothilone (Azathilone)

A green fluorescent 12‐aza‐epothilone (azathilone) derivative has been prepared through the attachment of the 4‐nitro‐2,1,3‐benzoxadiazole (NBD) fluorophore to the 12‐nitrogen atom of the azamacrolide core structure. While less potent than natural epothilones or different N12‐acylated azathilone derivatives, NBD‐azathilone ( 3 ) promotes tubulin assembly, inhibits cancer cell proliferation in vitro and arrests the cell cycle at the G2/M transition. Most significantly, the binding of 3 to cellular microtubules (MTs) could be directly visualized by confocal fluorescence microscopy. Based on competition binding experiments with laulimalide‐stabilized MTs in vitro, the N12‐Boc substituted azathilone 1 , Epo A, and NBD‐azathilone ( 3 ) all interact with the same tubulin‐binding site. Computational studies provided a structural model of the complexes between β‐tubulin and 1 or 3 , respectively, in which the NBD moiety of 3 or the BOC moiety of 1 directly and specifically contribute to MT binding. Collectively, these data demonstrate that the cellular effects of 3 and, by inference, also of other azathilones are the result of their interactions with the cellular MT network.     

Can a wastewater treatment plant be a powerplant? A case study

Today wastewater treatment plants are evaluated not only in terms of their treatment efficiency but also concerning their energy efficiency. Increasing energy efficiency can be realized either through operational optimisation or by realising an already existing potential for energy generation on-site. The main source of energy at a municipal wastewater treatment plant is the biogas produced in the anaerobic sludge digester. Studies indicate excess digester capacities of about 20% in Germany available for co-fermentation of organic substrates other than sewage sludge. This paper presents an example of a municipal wastewater treatment plant going towards an energy self-sufficient operation and even a surplus energy production as the result of an increasing co-fermentation of sludge from grease skimming tanks. In 2005 on average 113% of the electricity consumed for plant operation was generated on-site in gas engines. Co-fermentation of about 30% (related to the total dry residue input) of grease interceptor sludge in the presented case does not only effect a 4-times increased gas yield, but also an intensified 20% higher anaerobic degradation of the organic matter of the sewage sludge and thus having a positive influence not only on the energy and financial balance but also on the anaerobic sludge stabilisation with respect to the degradation degree of the organic fraction.     

Developing a culture of lifelong learning in a library environment

Between 1995 and 1996, the Annette and Irwin Eskind Biomedical Library (EBL) at Vanderbilt University Medical Center (VUMC) radically revised the model of service it provides to the VUMC community. An in-depth training program was developed for librarians, who began to migrate to clinical settings and establish clinical librarianship and information brokerage services beyond the library's walls. To ensure that excellent service would continue within the library, EBL's training program was adapted for library assistants, providing them with access to information about a wide variety of work roles and processes over a four to eight-month training period. Concurrently, customer service areas were reorganized so that any question--whether reference or circulation--could be answered at any of four service points, eliminating the practice of passing customers from person to person between the reference and circulation desks. To provide an incentive for highly trained library assistants to remain at EBL, management and library assistants worked together to redesign the career pathway based on defined stages of achievement, self-directed participation in library-wide projects, and demonstrated commitment to lifelong learning. Education and training were the fundamental principles at the center of all this activity.     

Single-center randomized trial comparing tacrolimus (FK506) and cyclosporine in the prevention of acute myocardial rejection

BACKGROUND: To compare the efficacy and safety of tacrolimus and cyclosporine in heart transplantation, this single-center, prospective, randomized, open-label clinical trial was undertaken. METHODS: Seventy-three adult patients were randomly assigned at the time of transplantation to receive either tacrolimus (n=43) or cyclosporine (n=30) as the primary immunosuppressant. Ten of the 43 patients in the tacrolimus group received the drug intravenously in the perioperative period; all other patients received only oral tacrolimus. RESULTS: With a mean follow-up of 27 months, patient survival rates (tacrolimus 83%, cyclosporine 81%) were similar. Fewer patients experienced acute rejection in the tacrolimus group (79%) than in the cyclosporine group (100%), but the difference was not statistically significant. The number of infections and dialysis and insulin requirements were similar for the 2 treatment groups, but the proportion of patients requiring multidrug antihypertensive regimens was lower in the tacrolimus group (12.5% vs 50.0% at month 6; p=.025). The interpatient variance in pharmacokinetic parameters in a subset of 10 patients was much higher after the first oral dose of tacrolimus than at steady-state (eg, first-dose time at which maximal concentration is reached (t(max)): 3.5+/-2.5h, steady-state t(max): 2.0+/-0.7h), and patients treated with intravenous tacrolimus (n=13) rather than oral tacrolimus (n=30) reached target concentrations faster and with less interpatient variability (eg, at day 0: 9.72+/-10.9 ng/mL intravenously vs 3.31+/-8.1 orally). CONCLUSIONS: Tacrolimus was associated with similar efficacy and safety profiles compared with cyclosporine. The higher interpatient variance in absorption associated with oral tacrolimus during the first few days after transplantation would suggest that intravenous tacrolimus should be used during the perioperative period.     

Effect of ethanol on postprandial duodenojejunal motility in humans

The effect of ethanol on postprandial small bowel motility was investigated in eight healthy volunteers using perfusion of nutrient solutions (17% proteins, 59% carbohydrates, 24% lipids) into the descending duodenum (5 ml/min for 120 min). An ethanol-containing solution (4% w/v, 4.06 kcal/min, 1190 mosmol/kg) was compared with the corresponding ethanol-free solution (2.64 kcal/min, 160 mosmol/kg) and another ethanol-free hyperosmolar solution adapted in caloric load and osmolality (4.06 kcal/min, 1160 mosmol/kg). Motility was recorded with a data logger and six pressure transducers at 3-cm intervals around the duodenojejunal flexure. Clustered contractions (27 +/- 4/hr) migrating aborally through the whole recording segment were the predominant motor pattern with ethanol compared with the ethanol-free (10 +/- 2/hr; P < 0.01) and the ethanol-free hyperosmolar solution (6 +/- 3/hr; P < 0.001). Other motility parameters with ethanol were not different from the ethanol-free solution, whereas the ethanol-free hyperosmolar solution showed a much less intense motor response. We conclude that ethanol does modify human postprandial duodenojejunal motility by inducing propagative motor patterns.