Modified starch as an excipient for pellets prepared by means of extrusion/spheronisation

De focus van dit onderzoeksproject zijn pellets als farmaceutische doseringsvorm. Pellets worden gedefiniëerd als sferische partikels met goede vloei-eigenschappen en met een nauwe deeltjesgroottedistributie (voor farmaceutische toepassingen variërend tussen 500 en 1500 μm). Als multiparticulaire doseringsvorm bieden pellets een aantal belangrijke voordelen ten opzichte van singleunit vormen zoals tabletten. Pellets kunnen via een aantal technieken worden geproduceerd: extrusie/sferonisatie, layering, directe pelletisatie en high-shear pelletisatie. Extrusie/sferonisatie, de techniek aangewend tijdens dit onderzoeksproject, bestaat uit een aantal verschillende stappen: in een eerste fase wordt een poedermengsel van het geneesmiddel en de hulpstoffen bevochtigd door toevoeging van een granulatievloeistof. Vervolgens wordt deze vochtige massa doorheen een extrusiescherm geperst (extrusie) waardoor cylindrische extrudaten worden gevormd. Deze worden daarna in kleinere cylindrische staafjes opgebroken en afgerond tot sferische granules (pellets) door middel van een roterende frictieplaat (sferonisatie). De laatste stap in het extrusie/sferonisatieproces is een droogfase. Op basis van literatuurgegevens is het duidelijk dat het controleren van de procesparameters tijdens de verschillende stappen van het proces essentieel is om de kwaliteit van de pellets te waarborgen

Direct Estimation of Parameters in ODE Models Using WENDy: Weak-form Estimation of Nonlinear Dynamics

We introduce the Weak-form Estimation of Nonlinear Dynamics (WENDy) method for estimating model parameters for non-linear systems of ODEs. Without relying on any numerical differential equation solvers, WENDy computes accurate estimates and is robust to large (biologically relevant) levels of measurement noise. For low dimensional systems with modest amounts of data, WENDy is competitive with conventional forward solver-based nonlinear least squares methods in terms of speed and accuracy. For both higher dimensional systems and stiff systems, WENDy is typically both faster (often by orders of magnitude) and more accurate than forward solver-based approaches. The core mathematical idea involves an efficient conversion of the strong form representation of a model to its weak form, and then solving a regression problem to perform parameter inference. The core statistical idea rests on the Errors-In-Variables framework, which necessitates the use of the iteratively reweighted least squares algorithm. Further improvements are obtained by using orthonormal test functions, created from a set of C-infinity bump functions of varying support sizes. We demonstrate the high robustness and computational efficiency by applying WENDy to estimate parameters in some common models from population biology, neuroscience, and biochemistry, including logistic growth, Lotka-Volterra, FitzHugh-Nagumo, Hindmarsh-Rose, and a Protein Transduction Benchmark model. Software and code for reproducing the examples is available at (https://github.com/MathBioCU/WENDy).Comment: 28 pages, 16 figure

Motivations for choosing librarianship as a second career among students at the University of British Columbia and the University of Hong Kong

The pathway to a career in the Library and Information Science field is rarely straightforward and unidirectional, but is often multi-faceted, with many circuitous detours along the way. There has been an increasing number of second-career in LIS emerging from many other non-LIS-related professions over the years. Many of these newcomers have made significant contributions to the LIS profession as they transfer their years of professional experiences, expertise, knowledge and skills from their former careers into the field. The purpose of this paper is to understand the perceptions and perspectives of the LIS students, and the various factors that influenced these midlife graduate students to consider switching from their current occupations to LIS as a second career.preprin

Support Systems Designed for Older Drivers to Achieve Safe and Comfortable Driving

Background: The number of older people is increasing. Many of them expect to maintain a rich social life and to continue driving at an older age. Objective: The present study investigates the mechanisms behind self-regulation and driving cessation in order to suggest development of support systems to prolong older drivers’ safe mobility. Method: Three focus groups were conducted with 19 older active drivers aged 65+ who were divided according to annual mileage driven. Results: A content analysis revealed broad self-regulatory behaviour as already reported in the literature, e.g., avoiding driving at rush hour and at night. The participants also reported difficulty in finding the way to their final destination and an increasing need to plan their travelling. Co-piloting was a behaviour applied by couples to cope with difficulties encountered in traffic. A large part of the discussion was focused on emerging feelings of stress, anxiety and fear when driving in recent years, a feeling induced by external factors e.g., other road users’ behaviour, traffic density or high speed. Apart from health problems, high levels of stress could explain driving cessation, especially for women. An increased feeling of safety and comfort could be achieved by an increased use of support systems specifically designed to respond to older drivers’ needs. Conclusion: Support systems for older drivers should increase comfort and decrease their stress levels. New systems, such as co-pilot function and more developed Global Positioning System (GPS) supporting of the entire travel from door to door, should be developed to respond to the market needs

Profiling of Phenolic Compounds and Antioxidant Activity of Dry Extracts from the Selected Sorbus Species

The antioxidant efficiency of dry extracts from inflorescences and/or leaves of seven Sorbus species was studied using four in vitro tests of SET (single electron transfer) and HAT-type (hydrogen atom transfer) mechanisms. The 70% methanol extracts and its diethyl ether, ethyl acetate, n-butanol and water fractions were tested in parallel with the phenolic standards, e.g., caffeic acid, quercetin, BHA, BHT, and TroloxÒ. The SET-type activity of the extracts depended primarily on the extraction solvent. The most valuable extracts were n-butanol and ethyl acetate ones, which activity was high in the DPPH (EC50 = 3.2–5.2 μg/mL), TEAC (2.8–4.0 mmol Trolox®/g), and FRAP (9.8–13.7 mmol Fe2+/g) tests, and strongly correlated with the total phenolic levels (39.6–58.2% of gallic acid equivalents). The HPLC-PDA analysis of the extracts led to the identification of chlorogenic acid, isoquercitrin, hyperoside, rutin, quercetin 3-O-sophoroside, and sexangularetin 3-O-b-D-glucopyranoside as the main components. Apart from flavonoids and hydroxycinnamic acids, proanthocyanidins have also a significant impact on the SET-type activity. The HAT-reactivity of the extracts in the linoleic acid peroxidation test (IC50 = 36.9–228.3 μg/mL) depended more strongly on the plant tissue than on the extraction solvent, and its correlation with the phenolic content was weak. Both SET and HAT-type activity of the most potent Sorbus extracts was comparable with the activity of the standards, indicating their great potential as effective sources for health products

High-speed imaging upgrade for a standard sample scanning atomic force microscope using small cantilevers

We present an atomic force microscope (AFM) head for optical beam deflection on small cantilevers. Our AFM head is designed to be small in size, easily integrated into a commercial AFM system, and has a modular architecture facilitating exchange of the optical and electronic assemblies. We present two different designs for both the optical beam deflection and the electronic readout systems, and evaluate their performance. Using small cantilevers with our AFM head on an otherwise unmodified commercial AFM system, we are able to take tapping mode images approximately 5-10 times faster compared to the same AFM system using large cantilevers. By using additional scanner turnaround resonance compensation and a controller designed for high-speed AFM imaging, we show tapping mode imaging of lipid bilayers at line scan rates of 100-500 Hz for scan areas of several micrometers in size

Chloroplast magnesium transporters play essential but differential roles in maintaining magnesium homeostasis

Magnesium (Mg2+) is essential for photosynthesis in the chloroplasts of land plants and algae. Being the central ion of chlorophyll, cofactor and activator of many photosynthetic enzymes including RuBisCO, magnesium-deficient plants may suffer from leaf chlorosis symptoms and retarded growth. Therefore, the chloroplast Mg2+ concentration is tightly controlled by magnesium transport proteins. Recently, three different transporters from two distinct families have been identified in the chloroplast inner envelope of the model plant Arabidopsis thaliana: MGT10, MGR8, and MGR9. Here, we assess the individual roles of these three proteins in maintaining chloroplast Mg2+ homeostasis and regulating photosynthesis, and if their role is conserved in the model green alga Chlamydomonas reinhardtii. Phylogenetic analysis and heterologous expression revealed that the CorC-like MGR8 and MGR9 transport Mg2+ by a different mechanism than the CorA-like MGT10. MGR8 and MGT10 genes are highest expressed in leaves, indicating a function in chloroplast Mg2+ transport. MGR9 is important for chloroplast function and plant adaptation in conditions of deficiency or excess of Mg2+. Transmission electron microscopy indicated that MGT10 plays a differential role in thylakoid stacking than MGR8 and MGR9. Furthermore, we report that MGR8, MGR9, and MGT10 are involved in building up the pH gradient across the thylakoid membrane and activating photoprotection in conditions of excess light, however the mechanism has not been resolved yet. While there are no chloroplast MGR-like transporters in Chlamydomonas, we show that MRS4 is a homolog of MGT10, that is required for photosynthesis and cell growth. Taken together, our findings reveal that the studied Mg2+ transporters play essential but differential roles in maintaining chloroplast Mg2+ homeostasis