Cloning and Functional Characterization of Dog OCT1 and OCT2: Another Step in Exploring Species Differences in Organic Cation Transporters

OCT1 and OCT2 are polyspecific membrane transporters that are involved in hepatic and renal drug clearance in humans and mice. In this study, we cloned dog OCT1 and OCT2 and compared their function to the human and mouse orthologs. We used liver and kidney RNA to clone dog OCT1 and OCT2. The cloned and the publicly available RNA-Seq sequences differed from the annotated exon-intron structure of OCT1 in the dog genome CanFam3.1. An additional exon between exons 2 and 3 was identified and confirmed by sequencing in six additional dog breeds. Next, dog OCT1 and OCT2 were stably overexpressed in HEK293 cells and the transport kinetics of five drugs were analyzed. We observed strong differences in the transport kinetics between dog and human orthologs. Dog OCT1 transported fenoterol with 12.9-fold higher capacity but 14.3-fold lower affinity (higher K_M) than human OCT1. Human OCT1 transported ipratropium with 5.2-fold higher capacity but 8.4-fold lower affinity than dog OCT1. Compared to human OCT2, dog OCT2 showed 10-fold lower transport of fenoterol and butylscopolamine. In conclusion, the functional characterization of dog OCT1 and OCT2 reported here may have implications when using dogs as pre-clinical models as well as for drug therapy in dogs.     

The Art of Masonry

Brick masonry is not only a question of building physics, building construction and durability, i.e. sustainability, but has much to do with aesthetics and making sense, which may have been forgotten in modern architecture with its absolute lack of décor. Masonry as an art form has been scarce since the era of brick expressionism. Recently, there have been some exceptions – and thoroughly welcome. The ”Fjordenhus“ in Vejle, Denmark, is an astonishing example.     

Scalable Functionalization of Optical Fibers Using Atomically Thin Semiconductors

Atomically thin transition metal dichalcogenides are highly promising for integrated optoelectronic and photonic systems due to their exciton-driven linear and nonlinear interactions with light. Integrating them into optical fibers yields novel opportunities in optical communication, remote sensing, and all-fiber optoelectronics. However, the scalable and reproducible deposition of high-quality monolayers on optical fibers is a challenge. Here, the chemical vapor deposition of monolayer MoS₂ and WS₂ crystals on the core of microstructured exposed-core optical fibers and their interaction with the fibers’ guided modes are reported. Two distinct application possibilities of 2D-functionalized waveguides to exemplify their potential are demonstrated. First, the excitonic 2D material photoluminescence is simultaneously excited and collected with the fiber modes, opening a novel route to remote sensing. Then it is shown that third-harmonic generation is modified by the highly localized nonlinear polarization of the monolayers, yielding a new avenue to tailor nonlinear optical processes in fibers. It is anticipated that the results may lead to significant advances in optical-fiber-based technologies.     

Automatic discovery of interpretable planning strategies

Machine Learning - When making decisions, people often overlook critical information or are overly swayed by irrelevant information. A common approach to mitigate these biases is to provide...     

Process variable implications for residual solvent removal and polymer morphology in the formation of gentamycin-loaded poly (L-lactide) microparticles

PURPOSE: The purpose was to determine the influence of process parameters in the precipitation with a compressed antisolvent (PCA) process on the morphology and residual dichloromethane (DCM) levels in gentamycin-loaded PLA microparticles. METHODS: The three variables studied were the rate of CO2 co-flowed during the polymer and drug post-precipitation, the post-precipitation pure CO2 flush rate, and the post-precipitation CO2 flush volume. Residual DCM levels were determined from headspace gas chromatography-mass spectroscopy (GC-MS) with single ion monitoring. X-ray diffraction (XRD) and differential scanning calorimetry (DSC) were used to estimate the crystallinity within microparticles. DCM was extracted from drug-loaded microparticles by both supercritical CO2 extraction and vacuum drying for up to two days to determine a lower limit for solvent removal. RESULTS: Increasing either the post-precipitations CO2 flow rate or flush volume resulted in lower residual DCM levels in the microparticle. The CO2 co-flow rate showed an opposite trend. Increasing in value resulted in a higher DCM value after precipitation. XRD and DSC analysis on these samples suggest that those produced at lower CO2 co-flow rates have a higher degree of crystallinity, which increases the diffusivity of DCM through the polymer matrix. Finally, samples subjected to extended (48 hr) CO2 extraction resulted in DCM levels on the order of one to three ppm. CONCLUSIONS: Specific PCA process conditions during microparticle formation have a strong influence on the residual solvent levels within the microparticles. Polymer morphology affects the diffusivity of solvent through the polymer matrix, which in turn determines the solvent removal rates.     

Finite-state Markov modeling of correlated Rician-fading channels

Stochastic properties of the binary channel that describe the successes and failures of the transmission of a modulated signal over a time-correlated flat-fading channel are considered for investigation. This analysis is employed to develop Kth-order Markov models for such a burst channel. The order of the Markov model that generates accurate analytical models is estimated for a broad range of fading environments. The parameterization and accuracy of an important class of hidden Markov models, known as the Gilbert-Elliott channel (GEC), are also investigated. Fading rates are identified in which the Kth-order Markov model and the GEC model approximate the fading channel with similar accuracy. The latter model is useful for approximating slowly fading processes, since it provides a more compact parameterization.