Modelling and experimental validation of a fluidized bed reactor freeboard region: application to natural gas combustion

A theoretical and experimental study of natural gas-air mixture combustion in a fluidized bed of sand particles is presented. The operating temperatures are lower than a critical temperature of 800 °C above which the combustion occurs in the vicinity of the fluidized bed. Our study focusses on the freeboard zone where most of the methane combustion takes place at such temperatures. Experimental results show the essential role of the projection zone in determining the global thermal efficiency of the reactor. The dense bed temperature, the fluidizing velocity and the mean particle diameter significantly affect the thermal behaviours. A model for natural gas-air mixture combustion in fluidized beds is proposed, counting for interactions between dense and dilute regions of the reactor [Pré et al. (1998)] supplemented with the freeboard region modelling of Kunii-Levenspiel (1990). Thermal exchanges due to the convection between gas and particles, and due to the conduction and radiation phenomena between the gas-particle suspension and the reactor walls are counted. The kinetic scheme for the methane conversion is that proposed by Dryer and Glassman (1973). Model predictions are in good agreement with the measurements

Ontogeny and cross species comparison of pathways involved in drug absorption, distribution, metabolism and excretion in neonates (review) : KIDNEY

The kidneys play an important role in many processes, including urine formation, water conservation, acid-base equilibrium, and elimination of waste. The anatomic and functional development of the kidney has different maturation time points in humans versus animals, with critical differences between species in maturation before and after birth. Absorption, distribution, metabolism, and excretion (ADME) of drugs vary depending on age and maturation, which will lead to differences in toxicity and efficacy. When neonate/juvenile laboratory animal studies are designed, a thorough knowledge of the differences in kidney development between newborns/children and laboratory animals is essential. The human and laboratory animal data must be combined to obtain a more complete picture of the development in the kidneys around the neonatal period and the complexity of ADME in newborns and children. This review examines the ontogeny and cross-species differences in ADME processes in the developing kidney in preterm and term laboratory animals and children. It provides an overview of insights into ADME functionality in the kidney by identifying what is currently known and which gaps still exist. Currently important renal function properties such as glomerular filtration rate, renal blood flow, and ability to concentrate are generally well known, while detailed knowledge about transporter and metabolism maturation is growing but is still lacking. Preclinical data in those properties is limited to rodents and generally covers only the expression levels of transporter or enzyme-encoding genes. More knowledge on a functional level is needed to predict the kinetics and toxicity in neonate/juvenile toxicity and efficacy studies

Letselschade Raad draait voor slachtoffers de klok meer dan twintig jaar terug:Analyse van handreiking zorgschade

De Handreiking Zorgschade en de daarin op te nemen Financiële paragraaf zijn in strijd met het geldende recht en het solidariteitsbeginsel, en met het wetsvoorstel dat de aanloop ertoe was. Dat is de conclusie van deze vier auteurs, die beargumenteren dat de keuzevrijheid van het letselschadeslachtoffer geheel is verdwenen, dat de voorgestelde tarieven op verschillende manieren niet kloppen, en dat de menselijke factor ontbreekt. Ze beginnen met een bespreking van de financieringsmogelijkheden van zorgschade, de jurisprudentie rond zorgschade en het wetsvoorstel Zorg- en affectieschade uit 2014. Daarna belichten ze de uitgangspunten van de Handreiking en de tarieven van de concept Financiële paragraaf. Ze vinden dat er onder de Handreiking een juridische bodem moet worden gelegd, met betrokkenheid van vertegenwoordigers van slachtoffers. Anders zou de wetgever alsnog moeten ingrijpen

Letselschade Raad draait voor slachtoffers de klok meer dan twintig jaar terug:Analyse van handreiking zorgschade

De Handreiking Zorgschade en de daarin op te nemen Financiële paragraaf zijn in strijd met het geldende recht en het solidariteitsbeginsel, en met het wetsvoorstel dat de aanloop ertoe was. Dat is de conclusie van deze vier auteurs, die beargumenteren dat de keuzevrijheid van het letselschadeslachtoffer geheel is verdwenen, dat de voorgestelde tarieven op verschillende manieren niet kloppen, en dat de menselijke factor ontbreekt. Ze beginnen met een bespreking van de financieringsmogelijkheden van zorgschade, de jurisprudentie rond zorgschade en het wetsvoorstel Zorg- en affectieschade uit 2014. Daarna belichten ze de uitgangspunten van de Handreiking en de tarieven van de concept Financiële paragraaf. Ze vinden dat er onder de Handreiking een juridische bodem moet worden gelegd, met betrokkenheid van vertegenwoordigers van slachtoffers. Anders zou de wetgever alsnog moeten ingrijpen

Treatment efficacy in a soman-poisoned guinea pig model: added value of physostigmine?

Current treatment of organophosphate poisoning is insufficient, and survivors may suffer from long-lasting adverse effects, such as cognitive deficits and sleep-wake disturbances. In the present study, we aimed at developing a guinea pig model to investigate the benefits of immediate and delayed stand-alone therapy on the development of clinical signs, EEG, heart rate, respiration and AChE activity in blood and brain after soman poisoning. The model allowed the determination of the therapeutic effects at the short-term of obidoxime, atropine and physostigmine. Obidoxime exerted the highest therapeutic efficacy at administration of the lowest dose (3.1 mg/kg i.m.), whereas two higher doses (9 and 18 mg/kg) were less effective on most parameters. Addition of atropine at 0.03 and 3 mg/kg (i.m.) to the treatment did not improve the therapeutic effects of obidoxime alone. Physostigmine (0.8 mg/kg im) at 1 min after poisoning increased mortality. Two lower doses (0.1 and 0.3 mg/kg i.m.) showed improvements on all parameters but respiration. The middle dose was most effective in preventing seizure development and therefore assessed as the most efficacious dose. Combined treatment of obidoxime and physostigmine shortened the duration of seizures, if present, from up to 80 min to ~10–15 min. In practice, treatment will be employed when toxic signs appear, with the presence of high levels of AChE inhibition in both blood and brain. Administration of physostigmine at that moment showed to be redundant or even harmful. Therefore, treatment of OP poisoning with a carbamate, such as physostigmine, should be carefully re-evaluated

Long-Term Survival of Human Neural Stem Cells in the Ischemic Rat Brain upon Transient Immunosuppression

Understanding the physiology of human neural stem cells (hNSCs) in the context of cell therapy for neurodegenerative disorders is of paramount importance, yet large-scale studies are hampered by the slow-expansion rate of these cells. To overcome this issue, we previously established immortal, non-transformed, telencephalic-diencephalic hNSCs (IhNSCs) from the fetal brain. Here, we investigated the fate of these IhNSC's immediate progeny (i.e. neural progenitors; IhNSC-Ps) upon unilateral implantation into the corpus callosum or the hippocampal fissure of adult rat brain, 3 days after global ischemic injury. One month after grafting, approximately one fifth of the IhNSC-Ps had survived and migrated through the corpus callosum, into the cortex or throughout the dentate gyrus of the hippocampus. By the fourth month, they had reached the ipsilateral subventricular zone, CA1-3 hippocampal layers and the controlateral hemisphere. Notably, these results could be accomplished using transient immunosuppression, i.e administering cyclosporine for 15 days following the ischemic event. Furthermore, a concomitant reduction of reactive microglia (Iba1+ cells) and of glial, GFAP+ cells was also observed in the ipsilateral hemisphere as compared to the controlateral one. IhNSC-Ps were not tumorigenic and, upon in vivo engraftment, underwent differentiation into GFAP+ astrocytes, and β-tubulinIII+ or MAP2+ neurons, which displayed GABAergic and GLUTAmatergic markers. Electron microscopy analysis pointed to the formation of mature synaptic contacts between host and donor-derived neurons, showing the full maturation of the IhNSC-P-derived neurons and their likely functional integration into the host tissue. Thus, IhNSC-Ps possess long-term survival and engraftment capacity upon transplantation into the globally injured ischemic brain, into which they can integrate and mature into neurons, even under mild, transient immunosuppressive conditions. Most notably, transplanted IhNSC-P can significantly dampen the inflammatory response in the lesioned host brain. This work further supports hNSCs as a reliable and safe source of cells for transplantation therapy in neurodegenerative disorders

Discovery of [11C]MK-6884: a positron emission tomography (PET) imaging agent for the study of M4 muscarinic receptor positive allosteric modulators (PAMs) in neurodegenerative diseases

The measurement of receptor occupancy (RO) using positron emission tomography (PET) has been instrumental in guiding discovery and development of CNS directed therapeutics. We and others have investigated muscarinic acetylcholine receptor 4 (M4) positive allosteric modulators (PAMs) for the treatment of symptoms associated with neuropsychiatric disorders. In this article, we describe the synthesis, in vitro, and in vivo characterization of a series of central pyridine-related M4 PAMs that can be conveniently radiolabeled with carbon-11 as PET tracers for the in vivo imaging of an allosteric binding site of the M4 receptor. We first demonstrated its feasibility by mapping the receptor distribution in mouse brain and confirming that a lead molecule 1 binds selectively to the receptor only in the presence of the orthosteric agonist carbachol. Through a competitive binding affinity assay and a number of physiochemical properties filters, several related compounds were identified as candidates for in vivo evaluation. These candidates were then radiolabeled with 11C and studied in vivo in rhesus monkeys. This research eventually led to the discovery of the clinical radiotracer candidate [11C]MK-6884

Multi-hit hypothesis in kidney development: Drug effects and interactions with extrauterine growth restriction

Contains fulltext : 160311.pdf (publisher's version ) (Open Access)RU Radboud Universiteit, 5 oktober 2016Promotor : Heuvel, L.P.W.J. van den Co-promotor : Schreuder, M.F

Future Inventors: An educational program to elicit problem solving skills in upper primary school learners in Lamu, Kenya

Science, Technology, Engineering and Mathematics (STEM) education plays a critical role in personal and societal development by preparing students for a rapidly changing, technological world. However, implementation of integrated STEM education poses significant challenges for educators, particularly in emerging markets such as Kenya, where resources and investments in teacher training are limited. In rural areas like the Lamu Archipelago, inadequate access to technology and educational resources intensifies this problem, leading to high dropout rates and limited opportunities for learners.IOMe005, a fabrication lab in Lamu county which is part of Kenya Red Cross Society, is looking to bridge the gap between primary school education and technological literacy for upper primary learners. The fabrication lab intends to train a team of innovators to facilitate a STEM program in local schools where learners are provided with tools to learn about STEM concept in an experiential way.The goal of this project is to create such a hands-on educational tool and teaching method which promotes problem-solving skills specifically, as this is a vital skill in the ever-changing world. The final design aims to empower a team of innovators to facilitate extracurricular Future Inventors workshops at Lamu primary schools, where they encourage upper primary learners to become the inventors of the future. In the Challenge-based workshops, learners are presented with a challenge, and can use the ThinkBricks, a set of building blocks, to build prototypes and envision solutions to these challenges. The program core is the Future Inventors manual, which guides the team of innovators step-by-step through the full process of development and facilitation of Future Inventors workshops.The Intercultural Design Approach was developed and employed during this project. The approach combines various design research activities such as Rapid Prototyping and participatory sessions, to bridge cultural gaps and mitigate the risks of unintended consequences that could negatively impact communities. Building cultural sensitivity, establishing relationships, and gaining a deep understanding of the context through field research were the core activities undertaken to learn about the culture and to design a solution that fits the targeted context.Integrated Product Desig