Evaluation of photografted charged sites within polymer monoliths in capillary columns using contactless conductivity detection

Capacitively coupled contactless conductivity detection (C4D) is presented as a novel and versatile means of visualising discrete zones of charged functional groups grafted onto polymer based monoliths. Monoliths were formed within 100 μm UV transparent fused silica capillaries and photografting methods were subsequently used to graft a charged functional monomer, 2-acrylamido-2-methyl-1-propanesulfonic acid (AMPS) onto discrete regions of the “generic” monolith using a photomask. Post-modification monolith evaluation involves scanning the C4D detector along the length of the monolith to obtain a profile of the exact spatial location of grafted charged functionalities with millimetre accuracy. The methodology was extended to the visualisation of several zones of immobilised protein (bovine serum albumin) using photografted azlactone groups to enable covalent attachment of the protein to the monolith at precise locations along its length. In addition, the extent of non-specific binding of protein to the ungrafted regions of the monolith due to hydrophobic interactions could be monitored as an increase in background conductivity of the stationary phase. Finally, the technique was cross-validated using fluorescence microscopy by immobilising green fluorescent protein (GFP) in discrete zones and comparing the profiles obtained using both complementary techniques

We Never Did This: A Framework for Measuring Novelty of Tasks in Mathematics Textbooks

Textbooks are an important resource in Irish mathematics classrooms, which can have both a positive and negative impact on teaching and learning. The Project Maths initiative is prompting teachers and students to cross boundaries and interact with mathematics in ways that had not been considered previously. Publishers have produced new texts in response to the expectations of the revised curriculum and the changed needs of the classroom. This paper presents a framework to consider the degree of novelty presented in tasks found in mathematics textbooks. Novelty is something that has been referred to, yet not addressed directly, in existing frameworks for the analysis of mathematical tasks. A particular strength of our framework is that it takes into account the experience of the solver, as opposed to just focusing on how a task has been structured. Sections of textbooks currently being used in Irish classrooms at second level have been analysed using this framework and the results indicate that while all textbooks incorporate a significant level of novelty, there is still room for more novel tasks to be included

A consideration of familiarity in Irish mathematics examinations

In this paper, we focus on the idea of familiarity and the differing levels of it that are apparent in Irish mathematics end of school state examination questions. We provide the results of an analysis of recent Higher Level and Ordinary Level Leaving Certificate mathematics examinations in terms of familiarity. Our findings do not indicate any particular recurring pattern evident in the levels of familiarity measured but generally not more than 20% of marks are allocated to unfamiliar questions

Algorithms for the solution of systems of coupled second order ordinary differential equations

The close-coupling approximation method involves the numerical solution of systems of coupled second order ordinary differential equations. The solutions can display instability which is made apparent by dependence of the resonance energy on H (step-size). This instability has been examined and corrected. The comparative efficiency, time-wise and storage-wise, of a number of algorithms for the integration of the system of equations is presented.<p

The Caterpillar Project: A Large Suite of Milky Way Sized Halos

We present the largest number of Milky Way sized dark matter halos simulated at very high mass ($\sim$$10^4$ M$_\odot$/particle) and temporal resolution ($\sim$5 Myrs/snapshot) done to date, quadrupling what is currently available in the literature. This initial suite consists of the first 24 halos of the $Caterpillar$ $Project$ (www.caterpillarproject.org) whose project goal of 60 - 70 halos will be made public when complete. We resolve $\sim$20,000 gravitationally bound subhalos within the virial radius of each host halo. Over the ranges set by our spatial resolution our convergence is excellent and improvements were made upon current state-of-the-art halo finders to better identify substructure at such high resolutions (e.g., on average we recover $\sim$4 subhalos in each host halo above 10$^8$ M$_\odot$ which would have otherwise not been found using conventional methods). For our relaxed halos, the inner profiles are reasonably fit by Einasto profiles ($\alpha$ = 0.169 $\pm$ 0.023) though this depends on the relaxed nature and assembly history of a given halo. Averaging over all halos, the substructure mass fraction is $f_{m,subs} = 0.121 \pm 0.041$, and mass function slope is d$N$/d$M\propto M^{-1.88 \pm 0.10}$ though we find scatter in the normalizations for fixed halo mass due to more concentrated hosts having less subhalos at fixed subhalo mass. There are no biases stemming from Lagrangian volume selection as all Lagrangian volume types are included in our sample. Our detailed contamination study of 264 low resolution halos has resulted in obtaining very large and unprecedented, high-resolution regions around our host halos for our target resolution (sphere of radius $\sim$$1.4 \pm 0.4$ Mpc) allowing for accurate studies of low mass dwarf galaxies at large galactocentric radii and the very first stellar systems at high redshift ($z \geq$ 10).Comment: 19 pages; 14 figures; 6 tables; Received September 3, 2015; Accepted November 15, 2015; Published February 2, 201

Training, status and migration of general practitioners / family physicians within Europe

The survey intended to explore and identify the training background and status of general practitioners/ family physicians (GPs) in member countries within EURACT (European Academy of Teachers in General Practice/Family Medicine), and to gain an overview of processes involved when GP-trained doctors migrate to work in another member country. A questionnaire, with closed and open-ended questions, was sent to representatives of all 39 EURACT-member countries in 2009. The main outcome measures were the training background and status of GPs in public/private settings in each country and the requirements of additional training and testing when migrating to another country. Forty-one completed questionnaires were received from 31 (79%) of the EURACT countries. The data indicate that specialist training for General Practice/ Family Medicine (GP/FM) is well established throughout and generally required for appointment to public career posts. The data also indicate that European Uniontrained GPs can move freely to most countries with usually no tests of medical knowledge or language proficiency. Orientation to the healthcare system in the destination country is usually not provided. work in public/private GP/FM posts in many European countries, although new appointments to public posts RESEARCH ARTICLE Training, status and migration of General Practitioners/Family Physicians within Europe in nearly all countries require specialist GP training. It was not possible to identify a uniform or agreed approach applied by employing agencies to confirm the medical competence and language skills of migrant doctors and to provide them with orientation to healthcare systems. In the high-context dependent discipline of GP/FM this is of concern.peer-reviewe

Toward the establishment of a standardized pre-clinical porcine model to predict food effects:Case studies on fenofibrate and paracetamol

A preclinical porcine model that reliably predicts human food effect of fenofibrate was developed. Fenofibrate was administered to pigs as model compound with a positive food effect. Two different types of fed conditions were explored: a FDA style breakfast and a standard pig pellet feed. In order to assess if complete stomach emptying had been achieved under the employed fasting protocol, the amount of gastric and intestinal content was evaluated post-mortem. In addition, the protocol was designed to evaluate gastric emptying in the pre- and postprandial state using paracetamol as a marker. The study confirmed that micronized fenofibrate displayed a positive food effect with a similar fold difference to humans in FDA style fed state. Post-mortem assessment of stomach and intestinal content confirmed significantly lower content in the fasted compared to the pig pellet fed state. In the case of paracetamol, a delayed gastric emptying in the fed state was not observed, which may suggest that the Magenstrasse phenomena reported in humans, may also occur in landrace pigs. The study demonstrated the utility of a food effect protocol in landrace pigs as a pre-clinical approach to predict human food effects and provided new insights into gastric emptying in pigs

Combining species specific in vitro &amp; in silico models to predict in vivo food effect in a preclinical stage – case study of Venetoclax

The pig has been increasingly used as a reliable preclinical model for assessing and predicting the in vivo bioavailability of different formulation strategies. Nevertheless, differences in the composition between porcine and human intestinal fluids, may impact on the solubility and dissolution behaviour of drugs, in particular BCS II/IV drugs. Recently, a porcine fasted simulated intestinal fluid (FaSSIFp) was developed to mimic the composition in the lumen of landrace pigs under fasted state conditions. In this work, we present the utilization of FaSSIFp to compare solubility against human FaSSIF & FeSSIF and further combine species specific in vitro testing with in silico predictive modelling. Venetoclax was chosen as a model drug, representing a BCS class IV drug, with a reported clinically significant positive food effect, where bioavailability is increased up to approximately five-fold when administered with a high-fat meal. Biorelevant species specific in vitro testing was a promising tool for integrating in vitro data into in silico models, using FaSSIFp resulted in reliable predictions of the plasma concentration profile in fasted pigs, based on a porcine physiologically based absorption model. The porcine physiologically based absorption model was used to prospectively simulate the impact of food on the bioavailability of venetoclax. The use of luminal solubility estimates in combination with dissolution data for venetoclax, measured in species specific simulated fluids, correctly predict the observed pig plasma concentration profile and food effect. Overall, integrating species specific in vitro – in silico models led to accurate prediction of in vivo absorption of venetoclax in a preclinical stage, which can support guidance in early decisions of drug product development. In addition, the study further demonstrated the utility of the pig model to predict the food effects of venetoclax in humans

Descendants of the first stars: the distinct chemical signature of second generation stars

Extremely metal-poor (EMP) stars in the Milky Way (MW) allow us to infer the properties of their progenitors by comparing their chemical composition to the metal yields of the first supernovae. This method is most powerful when applied to mono-enriched stars, i.e. stars that formed from gas that was enriched by only one previous supernova. We present a novel diagnostic to identify this subclass of EMP stars. We model the first generations of star formation semi-analytically, based on dark matter halo merger trees that yield MW-like halos at the present day. Radiative and chemical feedback are included self-consistently and we trace all elements up to zinc. Mono-enriched stars account for only $\sim 1\%$ of second generation stars in our fiducial model and we provide an analytical formula for this probability. We also present a novel analytical diagnostic to identify mono-enriched stars, based on the metal yields of the first supernovae. This new diagnostic allows us to derive our main results independently from the specific assumptions made regarding Pop III star formation, and we apply it to a set of observed EMP stars to demonstrate its strengths and limitations. Our results may provide selection criteria for current and future surveys and therefore contribute to a deeper understanding of EMP stars and their progenitors.Comment: 18 pages, 20 figures, published in MNRA