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.     

A Dynamic Risk Assessment Methodology for Maintenance Decision Support

The failure mode and effect analysis (FMEA) is a widely applied technique for prioritizing equipment failures in the maintenance decision‐making domain. Recent improvements on the FMEA have largely focussed on addressing the shortcomings of the conventional FMEA of which the risk priority number is incorporated as a measure for prioritizing failure modes. In this regard, considerable research effort has been directed towards addressing uncertainties associated with the risk priority number metrics, that is occurrence, severity and detection. Despite these improvements, assigning these metrics remains largely subjective and mostly relies on expert elicitations, more so in instances where empirical data are sparse. Moreover, the FMEA results remain static and are seldom updated with the availability of new failure information. In this paper, a dynamic risk assessment methodology is proposed and based on the hierarchical Bayes theory. In the methodology, posterior distribution functions are derived for risk metrics associated with equipment failure of which the posterior function combines both prior functions elicited from experts and observed evidences based on empirical data. Thereafter, the posterior functions are incorporated as input to a Monte Carlo simulation model from which the expected cost of failure is generated and failure modes prioritized on this basis. A decision scheme for selecting appropriate maintenance strategy is proposed, and its applicability is demonstrated in the case study of thermal power plant equipment failures. Copyright © 2016 John Wiley & Sons, Ltd.     

Fluorescence Lifetime Imaging Microscopy (FLIM) of Intracellular Transport by Means of Doubly Labelled siRNA Architectures

For monitoring the intracellular pathway of small interfering RNA (siRNA), both strands were labelled at internal positions by two ATTO dyes as an interstrand Förster resonance energy transfer pair. siRNA double strands show red emission and a short donor lifetime as readout, whereas siRNA antisense single strands show green emission and a long donor lifetime. This readout signals if GFP silencing can be expected (green) or not (red). We attached both dyes to three structurally different alkyne anchors by postsynthetic modifications. There is only a slight preference for the ribofuranoside anchors with the dyes at their 2’-positions. For the first time, the delivery and fate of siRNA in live HeLa cells was tracked by fluorescence lifetime imaging microscopy (FLIM), which revealed a clear relationship between intracellular transport using different transfection methods and knockdown of GFP expression, which demonstrates the potential of our siRNA architectures as a tool for future development of effective siRNA.     

Self-efficacy about information retrieval on the web across all domains: a short measure in French and English

Considering developments on the measurement of Internet Self-Efficacy literature, a short scale was developed with a focus on web searching across all domains. The Information Retrieval On the Web Self-Efficacy scale (IROWSE) was spread from the General Self-Efficacy Scale [Schwarzer, R. 1994. “Optimism, Vulnerability, and Self-Beliefs as Health Related Cognitions: A Systematic Overview.” Psychology and Health: An International 9: 161–180] and measures the value attributed by an individual to her/his own capacity to organise and execute information searches on the web. In study 1 (N?=?228), we aimed to ensure reliability, explore factorial structure, and check for criterion-related validity of a French form. In study 2 (N?=?534), we aimed to validate an English version among US and international (non-US) sample. From an internal validity point of view, both IROWSE versions turned out satisfactory with a one-factor model of eight items. As expected, the scales were not confused with self-esteem as a trait (study 1), self-reported Internet search skills (study 2) or general attitudes towards the Internet, and stemmed from direct experience with the Internet (study 1 and 2). Overall, slight differences between samples would indicate the cultural sensitivity of IROWSE measure encouraging running studies with a comparative approach. Resorting to the IROWSE measure might enhance the understanding of Internet practices, information retrieval behaviours, and search performance since self-efficacy would thus be assessed at a more domain-specific level.     

Asymmetrical Non-Uniform Heat Flux Distributions For Laminar Flow Heat Transfer With Mixed Convection In a Horizontal Circular Tube

Non-symmetric heat flux distributions in terms of gravity in solar collector tubes influence buoyancy-driven secondary flow which has an impact on the associated heat transfer and pressure drop performance. In this study the influence of the asymmetry angle (0°, 20°, 30° and 40°) with regard to gravity for non-uniform heat flux boundaries in a horizontal circular tube was investigated numerically. A stainless steel tube with an inner diameter of 62.68 mm, a wall thickness of 5.16 mm, and a length of 10 m was considered for water inlet temperatures ranging from 290 K to 360 K and inlet Reynolds numbers ranging from 130 to 2000. Conjugate heat transfer was modelled for different sinusoidal type outer surface heat flux distributions with a base-level incident heat flux intensity of 7.1 kW/m². It was found that average internal heat transfer coefficients increased with the circumferential span of the heat flux distribution. Average internal and axial local heat transfer coefficients and overall friction factors were at their highest for symmetrical heat flux cases (gravity at 0º) and lower for asymmetric cases. The internal heat transfer coefficients also increased with the inlet fluid temperature and decreased with an increase in the external heat loss transfer coefficient. Friction factors decreased with an increase in fluid inlet temperature or an increase in the external heat loss transfer coefficients of the tube model.     

Konzepte und Nachhaltigkeitsbewertung der Kohlenstoffkreislaufwirtschaft am Beispiel des chemischen Recyclings zur Olefinproduktion

The transformation of the current linear carbon economy to a circular carbon economy with chemical recycling of plastic waste and recirculation of domestic carbon resources is investigated using the example of petroleum-based olefin production. The scenario-based sustainability assessment shows the potential of chemical recycling to cover olefin production in Germany. With perspective 2050, the entire olefin production could be realized by coupling green e-hydrogen with previously incinerated non-fossil waste.     

Trends and patterns of PCB,DDE, and mercury contamination in bald eagle nestlings in the upper Midwest

We analyzed concentrations and trends of DDE, total PCBs, and mercury in bald eagle (Haliaeetus leucocephalus) nestlings at six study areas in the upper Midwest, 2006–2015, and long-term trends at two Lake Superior sites, 1989–2015. Eaglet plasma from the Apostle Islands in Lake Superior had the highest concentrations of DDE (geometric mean [GM]?=?10.6?μg/L), and DDE concentrations decreased at 5.8% per year across the region from 2006 to 2015, and at 5.5% per year at Lake Superior sites from 1989 to 2015. Concentrations of the sum of 75 PCB congeners (ΣPCB₇₅) were highest at Pools 3 and 4 of the Mississippi River (GM?=?114.8?μg/L) and did not decline significantly region-wide (all study areas together) between the years of 2006 and 2011. However, at Lake Superior, ΣPCB₇₅ declined from 1995 to 2011 along the south shore at 3.6% per year, with a non-significant decline at the Apostle Islands. Concentrations of mercury in nestling breast feathers were highest at the upper St. Croix River (GM?=?6.66?μg/g wet weight). At Lake Superior study areas, mercury declined at 1.6% per year from 1991 to 2015; however, from 2006 to 2015 we found no significant trend at one of these same study areas and mercury concentrations apparently increased at two study areas. Mean concentrations of contaminants were below levels associated with significant impairment of reproduction at all sites and mean reproductive rates were?>?1.4 young per nest. However, increasing concentrations of mercury in some areas, combined with relatively high concentrations at some nests, suggest that continued monitoring of mercury should be a management priority.     

Postnatal Smoke Exposure Further Increases the Hepatic Nicotine Metabolism in Prenatally Smoke Exposed Male Offspring and Is Linked with Aberrant Cyp2a5 Methylation

Prenatal smoke exposure (PreSE) is a risk factor for nicotine dependence, which is further enhanced by postnatal smoke exposure (PostSE). One susceptibility gene to nicotine dependence is Cytochrome P450 (CYP) 2A6, an enzyme responsible for the conversion of nicotine to cotinine in the liver. Higher CYP2A6 activity is associated with nicotine dependence and could be regulated through DNA methylation. In this study we investigated whether PostSE further impaired PreSE-induced effects on nicotine metabolism, along with Cyp2a5, orthologue of CYP2A6, mRNA expression and DNA methylation. Using a mouse model where prenatally smoke-exposed adult offspring were exposed to cigarette smoke for 3 months, enzyme activity, mRNA levels, and promoter methylation of hepatic Cyp2a5 were evaluated. We found that in male offspring, PostSE increased PreSE-induced cotinine levels and Cyp2a5 mRNA expression. In addition, both PostSE and PreSE changed Cyp2a5 DNA methylation in male groups. PreSE however decreased cotinine levels whereas it had no effect on Cyp2a5 mRNA expression or methylation. These adverse outcomes of PreSE and PostSE were most prominent in males. When considered in the context of the human health aspects, the combined effect of prenatal and adolescent smoke exposure could lead to an accelerated risk for nicotine dependence later in life.     

Physicochemical Properties of Injectable Hyaluronic Acid: Skin Quality Boosters

In addition to clinical research on the efficacy and compatibility of injectable hyaluronic acid (HA) based fillers, ample in vitro research on the physicochemical properties of these materials is published. Different HA-based product ranges are also available as skin quality boosters (SQBs) to improve skin quality. The aim of this study is to investigate the physicochemical properties of specific HAs for improving skin quality, as, to the best of the authors' knowledge, no data is published on this topic to date. This paper may provide a better understanding of clinical performance and differentiation between these SQBs. Five HA injectable hydrogels (Belotero Revive, Juvederm Volite, Restylane Skinbooster Vital, Viscoderm Hydrobooster, and Profilho) from the SQB product ranges of different companies and manufacturing technologies are investigated for their extrusion force, swelling degree, rheological performance, and cohesivity. There are significant differences in extrusion force, swelling degree, rheological performance, and cohesivity between the assessed SQBs. HA concentration (mg mL⁻¹) exhibits statistically significant positive correlations with extrusion force, swelling degree, tan delta, and cohesivity. This study provides a physicochemical characterization of different SQBs and information to improve understanding of this type of product.