Real-time observer model for Kraft wood digester.

Thesis (M.Sc.Eng.)-University of KwaZulu-Natal, 2005.At SAPPI-Tugela a continuous Kraft wood chip digester operates in EMCC mode (extended modified continuous cooking). Chips are initially exposed to a NaOH / Na2S liquor at high temperature in the top section. The chips move downward in plug flow passing circumferential screens used to draw liquor for various circulations. About midway down the spent black liquor is removed and the chips enter the cooler bottom section where some further reaction and washing occurs. Liquor level and chip level are maintained close to each other near the top. Chips require 8-12 hours to pass through the digester, depending on the chip feed rate. The key parameter of interest at the digester exit is the Kappa number, which is a measure of the extent of delignification which has occurred. Different board and paper products require different Kappa number pulp feed. (Final properties such as tensile, tear and bursting strengths will also depend on the way fibres have been modified in the digestion). The objective of this investigation is to predict the Kappa number of the product pulp in real-time, thus facilitating quicker reaction than the present dependence on laboratory analysis permits, possibly even allowing closed-loop control. The extent of delignification depends on liquor strength, temperature and exposure time, with final Kappa number also depending on the properties of the chip feed (wood type and moisture content). Compensation to maintain a steady Kappa number is made difficult by the long and varying residence time, and the fact that any changes apply to the whole profile held up in the digester. A number of static models for Kappa number prediction have been developed by previous workers, but these do not compare well with plant measurements. The collection of data from the Sappi-Tugela reactor, and the pulp quality reports, have been used to determine an efficient model. This step required a considerable data collection exercise, and similar results to the quality reports have been obtained using a simple linear model based on this data. The problem of model error is being reduced by arrangement as a Smith Predictor, in which the model is intermittently corrected by available laboratory analyses. At the same time, an interface was created, in order to synchronise measurement data for the chips presently leaving the reactor. In order to deal with the dead time, each parcel of chips entering the reactor is effectively tracked, and the changes in Kappa number integrated for reaction time under the varying conditions in transit. Knowing the present inventory of the reactor, this model can also be run forward in time as a predictive controller, to determine optimal control actions for maintenance of the target Kappa number

Wolbachia Interferes with Ferritin Expression and Iron Metabolism in Insects

Wolbachia is an intracellular bacterium generally described as being a facultative reproductive parasite. However, Wolbachia is necessary for oogenesis completion in the wasp Asobara tabida. This dependence has evolved recently as a result of interference with apoptosis during oogenesis. Through comparative transcriptomics between symbiotic and aposymbiotic individuals, we observed a differential expression of ferritin, which forms a complex involved in iron storage. Iron is an essential element that is in limited supply in the cell. However, it is also a highly toxic precursor of Reactive Oxygen Species (ROS). Ferritin has also been shown to play a key role in host–pathogen interactions. Measuring ferritin by quantitative RT-PCR, we confirmed that ferritin was upregulated in aposymbiotic compared to symbiotic individuals. Manipulating the iron content in the diet, we showed that iron overload markedly affected wasp development and induced apoptotic processes during oogenesis in A. tabida, suggesting that the regulation of iron homeostasis may also be related to the obligate dependence of the wasp. Finally, we demonstrated that iron metabolism is influenced by the presence of Wolbachia not only in the obligate mutualism with A. tabida, but also in facultative parasitism involving Drosophila simulans and in Aedes aegypti cells. In these latter cases, the expression of Wolbachia bacterioferritin was also increased in the presence of iron, showing that Wolbachia responds to the concentration of iron. Our results indicate that Wolbachia may generally interfere with iron metabolism. The high affinity of Wolbachia for iron might be due to physiological requirement of the bacterium, but it could also be what allows the symbiont to persist in the organism by reducing the labile iron concentration, thus protecting the cell from oxidative stress and apoptosis. These findings also reinforce the idea that pathogenic, parasitic and mutualistic intracellular bacteria all use the same molecular mechanisms to survive and replicate within host cells. By impacting the general physiology of the host, the presence of a symbiont may select for host compensatory mechanisms, which extends the possible consequences of persistent endosymbiont on the evolution of their hosts

Neuropeptide FF/neuropeptide AF receptors (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database

The Neuropeptide FF receptor family contains two subtypes, NPFF1 and NPFF2 (provisional nomenclature [10]), which exhibit high affinities for neuropeptide FF (NPFF, O15130) and RFamide related peptides (RFRP: precursor gene symbol NPVF, Q9HCQ7). NPFF1 is broadly distributed in the central nervous system with the highest levels found in the limbic system and the hypothalamus. NPFF2 is present in high density in the superficial layers of the mammalian spinal cord where it is involved in nociception and modulation of opioid functions

Neuropeptide FF/neuropeptide AF receptors in GtoPdb v.2023.1

The Neuropeptide FF receptor family contains two subtypes, NPFF1 and NPFF2 (provisional nomenclature [12]), which exhibit high affinities for neuropeptide FF (NPFF, O15130) and RFamide related peptides (RFRP: precursor gene symbol NPVF, Q9HCQ7). NPFF1 is broadly distributed in the central nervous system with the highest levels found in the limbic system and the hypothalamus. NPFF2 is present in high density in the superficial layers of the mammalian spinal cord where it is involved in nociception and modulation of opioid functions

Synthesis, biological evaluation, and SAR studies of 14β-phenylacetyl substituted 17-cyclopropylmethyl-7, 8-dihydronoroxymorphinones derivatives : Ligands with mixed NOP and opioid receptor profile

© 2018 Kumar, Polgar, Cami-Kobeci, Thomas, Khroyan, Toll and Husbands.A series of 14β-acyl substituted 17-cyclopropylmethyl-7,8-dihydronoroxymorphinone compounds has been synthesized and evaluated for affinity and efficacy for mu (MOP), kappa (KOP), and delta (DOP) opioid receptors and nociceptin/orphanin FQ peptide (NOP) receptors. The majority of the new ligands displayed high binding affinities for the three opioid receptors, and moderate affinity for NOP receptors. The affinities for NOP receptors are of particular interest as most classical opioid ligands do not bind to NOP receptors. The predominant activity in the [35S]GTPγS assay was partial agonism at each receptor. The results are consistent with our prediction that an appropriate 14β side chain would access a binding site within the NOP receptor and result in substantially higher affinity than displayed by the parent compound naltrexone. Molecular modeling studies, utilizing the recently reported structure of the NOP receptor, are also consistent with this interpretation.Peer reviewedFinal Published versio

Structural Requirements of N-Substituted Spiropiperidine Analogues as Agonists of Nociceptin/Orphanin FQ Receptor

The nociceptin/orphanin FQ (NOP) receptor is involved in a wide range of biological functions, including pain, anxiety, depression and drug abuse. Especially, its agonists have great potential to be developed into anxiolytics. In this work, both the ligand- and receptor-based three-dimensional quantitative structure–activity relationship (3D-QSAR) studies were carried out using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) techniques on 103 N-substituted spiropiperidine analogues as NOP agonists. The resultant optimal ligand-based CoMSIA model exhibited Q2 of 0.501, R2ncv of 0.912 and its predictive ability was validated by using an independent test set of 26 compounds which gave R2pred value of 0.818. In addition, docking analysis and molecular dynamics simulation (MD) were also applied to elucidate the probable binding modes of these agonists. Interpretation of the 3D contour maps, in the context of the topology of the active site of NOP, provided insight into the NOP-agonist interactions. The information obtained from this work can be used to accurately predict the binding affinity of related agonists and also facilitate the future rational design of novel agonists with improved activity

Adaptive preconditioning in neurological diseases -­ therapeutic insights from proteostatic perturbations

International audienceIn neurological disorders, both acute and chronic neural stress can disrupt cellular proteostasis, resulting in the generation of pathological protein. However in most cases, neurons adapt to these proteostatic perturbations by activating a range of cellular protective and repair responses, thus maintaining cell function. These interconnected adaptive mechanisms comprise a 'proteostasis network' and include the unfolded protein response, the ubiquitin proteasome system and autophagy. Interestingly, several recent studies have shown that these adaptive responses can be stimulated by preconditioning treatments, which confer resistance to a subsequent toxic challenge - the phenomenon known as hormesis. In this review we discuss the impact of adaptive stress responses stimulated in diverse human neuropathologies including Parkinson´s disease, Wolfram syndrome, brain ischemia, and brain cancer. Further, we examine how these responses - and the molecular pathways they recruit - might be exploited for therapeutic gai