Application of Polyimide-based Microfluidic Devices on Acid-catalyzed Hydrolysis of Dimethoxypropane

Microfluidic devices intensify transport phenomena and can improve chemical processes. New manufacturing processes and materials are perpetually developed due to constantly growing interest in process intensification. In this contribution, the authors present the design and application of polyimide-foil-based microfluidic mixing devices manufactured by reactive ion etching. As appropriate model reaction system, acid-catalyzed 2,2-dimethoxypropane (DMP) hydrolysis was chosen and investigated in three different mixing structure with varying flow rate. Energy dissipation rates were calculated to estimate mixing performances. The results show good mixing quality for Reynolds numbers between 10 and 100 and similar mixing times scales for all investigated microstructured mixers.     

Chemical Recycling of Carbon Fiber Reinforced Epoxy Composites Using Mild Conditions

The increased use of carbon fiber reinforced thermosets generates more waste and end-of-life products. However, an efficient recycling method for the expensive carbon fibers has not yet been developed. The selective decomposition of amine-cured epoxy resin under mild conditions is presented. A two-step method was investigated to decompose the epoxy resin. The optimum parameters were initially determined using a model compound. By analysis of the reaction products, a cleavage of the C–N bond according to the Cope elimination could be proven. Therefore, the Cope elimination is suggested as the main step of the decomposition of amine-cured epoxy resins in presence of hydrogen peroxide. By dissolving the resin, it is possible to recover resin-free fibers with unimpaired mechanical properties.     

Structure-Activity Relationship Explorations and Discovery of a Potent Antagonist for the Free Fatty Acid Receptor 2

Free fatty acid receptor 2 (FFA2) is a sensor for short-chain fatty acids that has been identified as an interesting potential drug target for treatment of metabolic and inflammatory diseases. Although several ligand series are known for the receptor, there is still a need for improved compounds. One of the most potent and frequently used antagonists is the amide-substituted phenylbutanoic acid known as CATPB ( 1 ). We here report the structure-activity relationship exploration of this compound, leading to the identification of homologues with increased potency. The preferred compound 37 (TUG-1958) was found, besides improved potency, to have high solubility and favorable pharmacokinetic properties.     

Hesperidin Promotes Osteogenesis and Modulates Collagen Matrix Organization and Mineralization In Vitro and In Vivo

This study evaluated the direct effect of a phytochemical, hesperidin, on pre-osteoblast cell function as well as osteogenesis and collagen matrix quality, as there is little known about hesperidin’s influence in mineralized tissue formation and regeneration. Hesperidin was added to a culture of MC3T3-E1 cells at various concentrations. Cell proliferation, viability, osteogenic gene expression and deposited collagen matrix analyses were performed. Treatment with hesperidin showed significant upregulation of osteogenic markers, particularly with lower doses. Mature and compact collagen fibrils in hesperidin-treated cultures were observed by picrosirius red staining (PSR), although a thinner matrix layer was present for the higher dose of hesperidin compared to osteogenic media alone. Fourier-transform infrared spectroscopy indicated a better mineral-to-matrix ratio and matrix distribution in cultures exposed to hesperidin and confirmed less collagen deposited with the 100-µM dose of hesperidin. In vivo, hesperidin combined with a suboptimal dose of bone morphogenetic protein 2 (BMP2) (dose unable to promote healing of a rat mandible critical-sized bone defect) in a collagenous scaffold promoted a well-controlled (not ectopic) pattern of bone formation as compared to a large dose of BMP2 (previously defined as optimal in healing the critical-sized defect, although of ectopic nature). PSR staining of newly formed bone demonstrated that hesperidin can promote maturation of bone organic matrix. Our findings show, for the first time, that hesperidin has a modulatory role in mineralized tissue formation via not only osteoblast cell differentiation but also matrix organization and matrix-to-mineral ratio and could be a potential adjunct in regenerative bone therapies.     

Is LRP2 Involved in Leptin Transport over the Blood-Brain Barrier and Development of Obesity?

The mechanisms underlying the transport of leptin into the brain are still largely unclear. While the leptin receptor has been implicated in the transport process, recent evidence has suggested an additional role of LRP2 (megalin). To evaluate the function of LRP2 for leptin transport across the blood-brain barrier (BBB), we developed a novel leptin-luciferase fusion protein (pLG), which stimulated leptin signaling and was transported in an in vitro BBB model based on porcine endothelial cells. The LRP inhibitor RAP did not affect leptin transport, arguing against a role of LRP2. In line with this, the selective deletion of LRP2 in brain endothelial cells and epithelial cells of the choroid plexus did not influence bodyweight, body composition, food intake, or energy expenditure of mice. These findings suggest that LRP2 at the BBB is not involved in the transport of leptin into the brain, nor in the development of obesity as has previously been described.     

Liver Lipids of Patients with Hepatitis B and C and Associated Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) still remains a difficult to cure malignancy. In recent years, the focus has shifted to lipid metabolism for the treatment of HCC. Very little is known about hepatitis B virus (HBV) and C virus (HCV)-related hepatic lipid disturbances in non-malignant and cancer tissues. The present study showed that triacylglycerol and cholesterol concentrations were similar in tumor adjacent HBV and HCV liver, and were not induced in the HCC tissues. Higher levels of free cholesterol, polyunsaturated phospholipids and diacylglycerol species were noted in non-tumorous HBV compared to HCV liver. Moreover, polyunsaturated phospholipids and diacylglycerols, and ceramides declined in tumors of HBV infected patients. All of these lipids remained unchanged in HCV-related HCC. In HCV tumors, polyunsaturated phosphatidylinositol levels were even induced. There were no associations of these lipid classes in non-tumor tissues with hepatic inflammation and fibrosis scores. Moreover, these lipids did not correlate with tumor grade or T-stage in HCC tissues. Lipid reprogramming of the three analysed HBV/HCV related tumors mostly resembled HBV-HCC. Indeed, lipid composition of non-tumorous HCV tissue, HCV tumors, HBV tumors and HBV/HCV tumors was highly similar. The tumor suppressor protein p53 regulates lipid metabolism. The p53 and p53S392 protein levels were induced in the tumors of HBV, HCV and double infected patients, and this was significant in HBV infection. Negative correlation of tumor p53 protein with free cholesterol indicates a role of p53 in cholesterol metabolism. In summary, the current study suggests that therapeutic strategies to target lipid metabolism in chronic viral hepatitis and associated cancers have to consider disease etiology.     

Placental Villous Explant Culture 2.0: Flow Culture Allows Studies Closer to the In Vivo Situation

During pregnancy, freely floating placental villi are adapted to fluid shear stress due to placental perfusion with maternal plasma and blood. In vitro culture of placental villous explants is widely performed under static conditions, hoping the conditions may represent the in utero environment. However, static placental villous explant culture dramatically differs from the in vivo situation. Thus, we established a flow culture system for placental villous explants and compared commonly used static cultured tissue to flow cultured tissue using transmission and scanning electron microscopy, immunohistochemistry, and lactate dehydrogenase (LDH) and human chorionic gonadotropin (hCG) measurements. The data revealed a better structural and biochemical integrity of flow cultured tissue compared to static cultured tissue. Thus, this new flow system can be used to simulate the blood flow from the mother to the placenta and back in the most native-like in vitro system so far and thus can enable novel study designs.     

Host Plant Constancy in Ovipositing Manduca sexta

Journal of Chemical Ecology - Many pollinating insects exhibit flower constancy, i.e. they target flower species they have already experienced and fed from. While the insects might profit from...     

Managing fire risk onboard offshore platforms: Lessons from Piper Alpha and probabilistic assessment of risk reduction measures

The offshore oil platform Piper Alpha was destroyed in July 1988 by a catastrophic fire. The causes of the accident included a combination of technical and organizational factors. In this paper, I describe the accident, its chronology, and the dependencies involved. I then examine some of the human errors that led to the disaster and their organizational roots, such as economic pressures, the permit-to-work system, and the inadequacy of regulatory oversight in the United Kingdom at the time of the accident. Risk-reduction measures can be costly, however, and priorities must be set based on costs and benefits. To this end, I describe a probabilistic risk analysis model that can be used to assess the benefits of different fire safety measures, focusing on reinforcing the emergency water pumps.     

The Conditions for Se-Enzymes,NO, cGMP and LDL to be Formed and How They are Connected with Each Other

Transportation of energy and substances is fundamental for the conditions of life. The energy from metabolised food is yielded at the reduction of oxygen by the assistance of Se-enzymes. Activated Se-enzymes contain an electron conducting Se-link with elemental Se bounded to Se-cys （Se-cystein） that prevents electron transferring （autoxidable） agents, as arginine, from oxidations. NO is formed from e.g. arginine during the passive state of a Se-enzyme. With NO, instead of O2, bounded to a hem group, destroying oxidations are avoided. This is the role of NO. A nerve signal is activated by the GTP （guanosine triphosphate）-induced triggered transformation of cGMP （cyclic guanosine monophosphate） into GMP, closing the sodium channels. When GTP is consumed, the opposite reaction takes place. The direct influence of the GMP/cGMP quote on a nerve signal makes GMP/cGMP equal to EDHF （endothelium-derived hyperpolarizing factor）. Part of the energy from food is stored and transported in the form of acetyl groups, building up many important molecules of which LDL （low density lipoprotein） is one, containing cholesteryl esters. These are brought in to the cell, decomposed to acetyl groups generating hydrogen, H, making LDL to an essential substance. High levels are connected to impaired energy yielding reactions, perhaps related to low levels of some substances, especially to one or both forms of Se. The necessity of a Se-link and NO induced protection against oxidations by reducible oxygen can no longer be neglected.