Transfer Learning Aurora Image Classification and Magnetic Disturbance Evaluation.

We develop an open source algorithm to apply Transfer learning to Aurora image classification and Magnetic disturbance Evaluation (TAME). For this purpose, we evaluate the performance of 80 pretrained neural networks using the Oslo Auroral THEMIS (OATH) data set of all-sky images, both in terms of runtime and their features' predictive capability. From the features extracted by the best network, we retrain the last neural network layer using the Support Vector Machine (SVM) algorithm to distinguish between the labels "arc," "diffuse," "discrete," "cloud," "moon" and "clear sky/ no aurora". This transfer learning approach yields 73% accuracy in the six classes; if we aggregate the 3 auroral and 3 non-aurora classes, we achieve up to 91% accuracy. We apply our classifier to a new dataset of 550,000 images and evaluate the classifier based on these previously unseen images. To show the potential usefulness of our feature extractor and classifier, we investigate two test cases: First, we compare our predictions for the "cloudy" images to meteorological data and second we train a linear ridge model to predict perturbations in Earth's locally measured magnetic field. We demonstrate that the classifier can be used as a filter to remove cloudy images from datasets and that the extracted features allow to predict magnetometer measurements. All procedures and algorithms used in this study are publicly available, and the code and classifier are provided, which opens possibility for large scale studies of all-sky images.

Ophthalmic drug delivery systems--recent advances.

Eye-drops are the conventional dosage forms that account for 90% of currently accessible ophthalmic formulations. Despite the excellent acceptance by patients, one of the major problems encountered is rapid precorneal drug loss. To improve ocular drug bioavailability, there is a significant effort directed towards new drug delivery systems for ophthalmic administration. This chapter will focus on three representative areas of ophthalmic drug delivery systems: polymeric gels, colloidal systems, cyclodextrins and collagen shields. Hydrogels generally offer a moderate improvement of ocular drug bioavailability with the disadvantage of blurring of vision. In situ activated gel-forming systems are preferred as they can be delivered in drop form with sustained release properties. Colloidal systems including liposomes and nanoparticles have the convenience of a drop, which is able to maintain drug activity at its site of action and is suitable for poorly water-soluble drugs. Among the new therapeutic approaches in ophthalmology, cyclodextrins represent an alternative approach to increase the solubility of the drug in solution and to increase corneal permeability. Finally, collagen shields have been developed as a new continuous-delivery system for drugs that provide high and sustained levels of drugs to the cornea, despite a problem of tolerance. It seems that new tendency of research in ophthalmic drug delivery systems is directed towards a combination of several drug delivery technologies. There is a tendency to develop systems which not only prolong the contact time of the vehicle at the ocular surface, but which at the same time slow down the elimination of the drug. Combination of drug delivery systems could open a new directive for improving results and the therapeutic response of non-efficacious systems.

Clinical pharmacokinetics of levorotatory and racemic disopyramide, at steady state, following oral administration in patients with ventricular arrhythmias.

Electrophysiological effects, antiarrhythmic activity and kinetics of levorotatory disopyramide (R(-) DP) and racemic disopyramide (equimolar mixture of R(-) DP and S(+) DP) were compared in patients with ventricular arrhythmias. This double blind cross-over randomized trial was achieved, at steady-state, following oral administration of 200 mg three times a day. In comparison with baseline values, electrophysiological data indicated that R(-) DP and racemic DP prolonged, significantly and similarly, PR interval (+11.7% and +10%, respectively, P less than .01), and QTc interval (+9.2% and +7%, respectively, P less than .001), while QRS interval was not significantly affected. The antiarrhythmic activity, assessed by percent reduction in ventricular extrasystoles frequency, showed a similar efficiency of levorotatory and racemic DP: 80% and 74%, respectively (P = .24). Ventricular tachycardias disappeared with both treatments in the three patients concerned. During the racemic period, the mean total plasma clearance, expressed as CL/F, of S(+) DP (114.6 ml/min), was significantly lower than that of R(-) DP (157 ml/min), (P less than .001). The mean total plasma clearance of R(-) DP, during the levorotatory period (163 ml/min), did not differ from the respective value determined during the racemic period (P = .32). During the racemic period, the stereoselective difference in total plasma clearances, which is not observed when DP enantiomers are administered separately, may result from an increase in unbound fraction of R(-) DP, due to the presence of S(+) DP, which is known to be a potent displacer of R(-) DP.

Approaches to understanding the functional architecture of the plant cell wall.

Cell wall polysaccharides are some of the most complex biopolymers known, and yet their functions remain largely mysterious. Advances in imaging methods permit direct visualisation of the molecular architecture of cell walls and the modifications that occur to polymers during growth and development. To address the structural and functional relationships of individual cell wall components, we need to better characterise a broad range of structural and architectural alterations in cell walls, appearing as a consequence of developmental regulation, environmental adaptation or genetic modification. We have developed a rapid method to screen large numbers of plants for a broad range of cell wall phenotypes using Fourier transform infrared microspectroscopy and Principal Component Analysis. We are using model systems to uncover the genes that encode some of the cell-wall-related biosynthetic and hydrolytic enzymes, and structural proteins.

Disposition kinetics and oral bioavailability of vincamine-loaded polyalkyl cyanoacrylate nanoparticles.

Hexyl cyanoacrylate nanoparticles loaded with vincamine as a drug model were prepared. Disposition kinetics and oral bioavailability of vincamine in rabbits were compared after administration of an aqueous solution of the drug and an aqueous colloidal suspension of nanoparticles. After intravenous administration, total body clearance of vincamine was equal for both dosage forms, but a longer half-life (X 2) and larger distribution volume (X 2) were observed with the suspension of nanoparticles. After oral administration, the bioavailability of vincamine was considerably greater for the drug loaded onto nanoparticles.

Identification of Listeria monocytogenes from unpasteurized apple juice using rapid test kits.

A microbiological survey of 50 retail juices was conducted in the fall of 1996. These juices were analyzed for Listeria monocytogenes, Escherichia coli O157:H7, Salmonella, coliforms, fecal coliforms, and pH. Two unpasteurized juices were positive for L. monocytogenes: an apple juice and an apple raspberry blend with a pH of 3.78 and 3.75, respectively. Three L. monocytogenes isolates were characterized. The colonies were typical for Listeria sp. on Oxford and lithium chloride-phenylethanol-moxalactam agars and were beta-hemolytic on sheep blood agar. The isolates required 5 days of incubation at 35 degrees C to produce a positive rhamnose reaction in a phenol red carbohydrate broth. This slow rhamnose utilization resulted in these isolates not being identified using the Micro-ID test strip (Organon Technika). However, the isolates were positive for L. monocytogenes using the API Listeria strip (BioMerieux) and a multiplex polymerase chain reaction for detection of the hemolysis (hyla) and invasion-associated protein (iap) genes.

Preparation and in vivo studies of a new drug delivery system. Nanoparticles of alkylcyanoacrylate.

Polyhexylcyanoacrylate nanoparticles have been prepared with vincamine as the model drug. These particles had an average size of 200 nm and adsorbed approximately 43% of vincamine. The adsorption of vincamine to nanoparticles modified the distribution of vincamine in tissues. After iv injection the distribution volumes were increased in comparison with an aqueous solution of drug. In comparison with an aqueous solution of drug, the absolute bioavailability of vincamine was also increased after an oral administration of nanoparticles.

Human pharmacokinetics and metabolism of disopyramide enantiomers.

The objective of the present study was to investigate human pharmacokinetics and metabolism of disopyramide (DP) enantiomers. Six healthy male volunteers entered the study. They were given, separately and via oral route, as repeated doses for 5 days, R(-) DP and S(+) DP at a dose of 100 mg twice daily. Unbound fractions of DP and metabolite (MND) enantiomers were obtained on each plasma sample, i.e. ex vivo, using ultrafiltration. Pharmacokinetic parameters of DP enantiomers based on total plasma concentrations were not significantly different. On the other hand, unbound pharmacokinetic parameters displayed marked stereoselectivity. The mean unbound clearance of R(-) DP and S(+) DP were 8.59 and 14.9 ml/min/kg, respectively (p = 0.003). The mean unbound renal clearance of R(-) DP and S(+) DP were 6.26 and 8.75 ml/min/kg, respectively (p = 0.025). The non renal clearance of R(-) DP and S(+) DP averaged 2.32 and 6.19 ml/min/kg, respectively (p = 0.002). The mean unbound volume of distribution of R(-) and S(+) DP were 225 and 381 liters, respectively (p = 0.023). The half-life of R(-) DP and S(+) DP averaged 4.17 and 3.91 hr, respectively (p = 0.21). The unbound fraction at steady-state of R(-) DP and S(+) DP averaged 12.5 and 7.5%, respectively (p = 0.002). In vitro binding experiments, performed for each subject, allowed to indicate that the stereoselective plasma binding was due to a stereoselective affinity, the binding capacity of both enantiomers being the same. Pharmacokinetic data emphasized the influence of stereoselectivity in the human disposition of DP enantiomers.(ABSTRACT TRUNCATED AT 250 WORDS)

[The effect of chirality in clinical pharmacology]. / Influence de la chiralité en pharmacologie clinique.

Many drugs have one or more asymmetric centres and are used as a racemate: equimolar mixture of enantiomers. Drug enantiomers may interact differently with biological macromolecules. Hence, the influence of chirality in relation to pharmacokinetics and pharmacodynamics needs to be studied. Many pharmacokinetic and pharmacodynamic examples stress on the major influence of chirality. The valuable knowledge acquired from such studies can lead to a better understanding of drug interactions and mechanisms of drug action and to an optimization of drug therapy either by a better use of still marketed racemate drugs of by the development of pure enantiomers.

[The effect of modification of excipients for the bioavailability of vinburnine]. / Influence d'une modification d'excipients sur la biodisponibilité de la vinburnine.

Biopharmaceutic comparison is achieved between commercialized capsules of vinburnine and a new dosage form. The difference between the two drug products concerns only the quality of excipients. Drug bioavailability decreases of about 10%, in despite of the very important, and well known, interindividual variations of vincamine drug products. Only the absorption rate seems statistically lightly decreased by the new formulation.

[The oral liquid form of vinburnine: biopharmaceutics]. / Forme buvable de vinburnine: une approche biopharmaceutique.

Biopharmaceutic comparison is achieved between commercialized capsules of vinburnine and drops dosage form intended for geriatric pharmacotherapy. Drug bioavailability of vinburnine seems saved, if not significantly increased by the new formulation, in spite of the very important, and well known interindividual variations of vincamine drug products. Only the absorption rate seems statistically increased by drops.

[Absolute and relative bioavailability of germanium in the rabbit]. / Biodisponibilités absolue et relative du germanium chez le lapin.

The debated consumption of germanium suggested the authors to compare biopharmaceutical parameters of germanium oxide and germanium sesquioxide. A first evaluation, in rabbit, has been based on Germanium blood levels determined by atomic absorption spectrometry, after cross administration of both products by the I.V. and oral routes. When given orally, the apparent oxide bioavailability is very low (about 10%) but better than that of the sesquioxide. That difference could result from differences of disposition parameters of both products, which have to be studied late.