Adaptive Linear Dynamic Matrix Control applied to an integrating process

Dynamic Matrix Control (DMC) has proven to be a powerful tool for optimal regulation of chemical processes under constrained conditions. It is based on a linear convolution model derived from step-response measurements. A model predictive control algorithm optimises closed-loop performance for a nominal operating point. However, as the process moves away from this point, control usually becomes sub-optimal due to process non-linearity. As seen in this work, the DMC algorithm can be made adaptive, to establish a new local model, by recursive estimation of the local step response parameters from normal plant variations. However, when used for control of plants containing integrating process units, steady-state offsets occur for sustained changes. Thus, a novel Adaptive Linear Dynamic Matrix Control (ALDMC) algorithm has been developed and used to control a 2-input/2-output system with an integrating behaviour. Comparisons of model control and plant control with and without these features demonstrated the importance of integral compensation for integrating processes, and model adaptation in the case of plant/model mismatch. Some cross-compensation of integration by the adaptive feature was also noted. An holistic technique is demonstrated which simultaneously recognises residual integration disturbances and matrix parameter variations, whereas previous techniques which recognise only one of these will fail in the presence of the other.     

Azaaurones as Potent Antimycobacterial Agents Active against MDR- and XDR-TB

Herein we report the screening of a small library of aurones and their isosteric counterparts, azaaurones and N-acetylazaaurones, against Mycobacterium tuberculosis. Aurones were found to be inactive at 20 μm , whereas azaaurones and N-acetylazaaurones emerged as the most potent compounds, with nine derivatives displaying MIC₉₉ values ranging from 0.4 to 2.0 μm . In addition, several N-acetylazaaurones were found to be active against multidrug-resistant (MDR) and extensively drug-resistant (XDR) clinical M. tuberculosis isolates. The antimycobacterial mechanism of action of these compounds remains to be determined; however, a preliminary mechanistic study confirmed that they do not inhibit the mycobacterial cytochrome bc1 complex. Additionally, microsomal metabolic stability and metabolite identification studies revealed that N-acetylazaaurones are deacetylated to their azaaurone counterparts. Overall, these results demonstrate that azaaurones and their N-acetyl counterparts represent a new entry in the toolbox of chemotypes capable of inhibiting M. tuberculosis growth.     

Untersuchung von lokalen Schichtdickenverteilungen in Fluiden mithilfe der Nahinfrarot‐Bildanalyse

An online image analysis method to determine the film thickness in fluids by use of pulsed near infrared LEDs and an NIR camera was developed. This technique offers the possibility to monitor moving fluid layers. In this work the possibilities and limits of the used apparatus are demonstrated with the application example of measurement of the fluid film thickness distribution of water and glycerol in a falling film.     

Inkjet printing of photocatalytically active TiO2 thin films from water based precursor solutions

In this work, aqueous chemical solution deposition route suited for inkjet printing is used for the synthesis of photocatalytically active TiO₂ coatings. Environmentally friendly precursor solutions with electromagnetic ink-jet printing, allows cheap and simple processing of TiO₂ films on glass. The hydrolysis reaction of water sensitive titanium alkoxide (Ti-alkoxide) precursor is controlled by adding complexing agents as citric acid and triethanolamine prior to water addition, and aqueous stable solutions are achieved. The pH of the solutions is brought to neutral to guarantee flexible processing, avoid damage to substrates and equipment. Solution parameters are adapted to obtain optimal gelation conditions and good jettability. The influence of processing parameters on the phase formation and surface morphology is studied by thermogravimetric analysis and differential thermal analysis (TGA/DTA), X-ray diffraction (XRD), scanning electron microscopy (SEM) and atomic force microscopy (AFM). The photocatalytic activity of the films is evaluated by the degradation of methyl orange.     

Effect of ethanol administration on fatty acid desaturation

The effect of ethanol on the fatty acid desaturation by rat liver has been studied using liquid diets of different composition. Acute ethanol administration increased triacylglycerols of total liver lipids, but did not modify significantly the lipidic composition of microsomes. The Δ6 and Δ5 desaturases were inhibited by ethanol whereas the Δ9 desaturase and fatty acid synthetase were apparently modified only by diet composition. NADH-cytochrome (cyt.) c reductase was partially inhibited, whereas NADH-cyt. b₅ reductase remained practically unaltered and NADPH-cyt. c reductase activity was enhanced. Decreased electrons supplied by the microsomal cyt. b₅ electron transport chain would not be the reason for the inhibition of Δ6 and Δ5 desaturases by ethanol.     

Novel Tacrine‐Grafted Ugi Adducts as Multipotent Anti‐Alzheimer Drugs: A Synthetic Renewal in Tacrine–Ferulic Acid Hybrids

Herein we describe the design, multicomponent synthesis, and biological, molecular modeling and ADMET studies, as well as in vitro PAMPA‐blood–brain barrier (BBB) analysis of new tacrine–ferulic acid hybrids (TFAHs). We identified (E)‐3‐(hydroxy‐3‐methoxyphenyl)‐N‐{8[(7‐methoxy‐1,2,3,4‐tetrahydroacridin‐9‐yl)amino]octyl}‐N‐[2‐(naphthalen‐2‐ylamino)2‐oxoethyl]acrylamide (TFAH 10 n ) as a particularly interesting multipotent compound that shows moderate and completely selective inhibition of human butyrylcholinesterase (IC₅₀=68.2 nM ), strong antioxidant activity (4.29 equiv trolox in an oxygen radical absorbance capacity (ORAC) assay), and good β‐amyloid (Aβ) anti‐aggregation properties (65.6 % at 1:1 ratio); moreover, it is able to permeate central nervous system (CNS) tissues, as determined by PAMPA‐BBB assay. Notably, even when tested at very high concentrations, TFAH 10 n easily surpasses the other TFAHs in hepatotoxicity profiling (59.4 % cell viability at 1000 μM ), affording good neuroprotection against toxic insults such as Aβ_1–40, Aβ_1–42, H₂O₂, and oligomycin A/rotenone on SH‐SY5Y cells, at 1 μM . The results reported herein support the development of new multipotent TFAH derivatives as potential drugs for the treatment of Alzheimer′s disease.     

Antitumor Activity of Ionic Liquids Based on Ampicillin

Significant antiproliferative effects against various tumor cell lines were observed with novel ampicillin salts as ionic liquids. The combination of anionic ampicillin with appropriate ammonium, imidazolium, phosphonium, and pyridinium cations yielded active pharmaceutical ingredient ionic liquids (API‐ILs) that show potent antiproliferative activities against five different human cancer cell lines: T47D (breast), PC3 (prostate), HepG2 (liver), MG63 (osteosarcoma), and RKO (colon). Some API‐ILs showed IC₅₀ values between 5 and 42 nM , activities that stand in dramatic contrast to the negligible cytotoxic activity level shown by the ampicillin sodium salt. Moreover, very low cytotoxicity against two primary cell lines—skin (SF) and gingival fibroblasts (GF)—indicates that the majority of these API‐ILs are nontoxic to normal human cell lines. The most promising combination of antitumor activity and low toxicity toward healthy cells was observed for the 1‐hydroxyethyl‐3‐methylimidazolium–ampicillin pair ([C₂OHMIM][Amp]), making this the most suitable lead API‐IL for future studies.     

BMP9-Induced Survival Effect in Liver Tumor Cells Requires p38MAPK Activation

The study of bone morphogenetic proteins (BMPs) role in tumorigenic processes, and specifically in the liver, has gathered importance in the last few years. Previous studies have shown that BMP9 is overexpressed in about 40% of hepatocellular carcinoma (HCC) patients. In vitro data have also shown evidence that BMP9 has a pro-tumorigenic action, not only by inducing epithelial to mesenchymal transition (EMT) and migration, but also by promoting proliferation and survival in liver cancer cells. However, the precise mechanisms driving these effects have not yet been established. In the present work, we deepened our studies into the intracellular mechanisms implicated in the BMP9 proliferative and pro-survival effect on liver tumor cells. In HepG2 cells, BMP9 induces both Smad and non-Smad signaling cascades, specifically PI3K/AKT and p38MAPK. However, only the p38MAPK pathway contributes to the BMP9 growth-promoting effect on these cells. Using genetic and pharmacological approaches, we demonstrate that p38MAPK activation, although dispensable for the BMP9 proliferative activity, is required for the BMP9 protective effect on serum withdrawal-induced apoptosis. These findings contribute to a better understanding of the signaling pathways involved in the BMP9 pro-tumorigenic role in liver tumor cells.