The synthesis and antithrombotic activity of a series of nonpeptide bicyclic thrombin inhibitors is described. We have explored the SAR with modifications to the P1 site. The introduction of arginine mimetics at the P1 site led to potent and selective thrombin inhibitors. 相似文献
Context: Ethylcellulose is commonly dissolved in a solvent or formed into an aqueous dispersion and sprayed onto various dosage forms to form a barrier membrane to provide controlled release in pharmaceutical formulations. Due to the variety of solvents utilized in the pharmaceutical industry and the importance solvent can play on film formation and film strength it is critical to understand how solvent can influence these parameters.
Objective: To systematically study a variety of solvent blends and how these solvent blends influence ethylcellulose film formation, physical and mechanical film properties and solution properties such as clarity and viscosity.
Materials and methods: Using high throughput capabilities and evaporation rate modeling, thirty-one different solvent blends composed of ethanol, isopropanol, acetone, methanol, and/or water were formulated, analyzed for viscosity and clarity, and narrowed down to four solvent blends. Brookfield viscosity, film casting, mechanical film testing and water permeation were also completed.
Results and discussion: High throughput analysis identified isopropanol/water, ethanol, ethanol/water and methanol/acetone/water as solvent blends with unique clarity and viscosity values. Evaporation rate modeling further rank ordered these candidates from excellent to poor interaction with ethylcellulose. Isopropanol/water was identified as the most suitable solvent blend for ethylcellulose due to azeotrope formation during evaporation, which resulted in a solvent-rich phase allowing the ethylcellulose polymer chains to remain maximally extended during film formation. Consequently, the highest clarity and most ductile films were formed.
Conclusion: Employing high throughput capabilities paired with evaporation rate modeling allowed strong predictions between solvent interaction with ethylcellulose and mechanical film properties. 相似文献
Oxygen sensing films were synthesized by a chemical conjugation of functional platinum porphyrin probes in silica gel, polystyrene (PS), and poly(2-hydroxyethyl methacrylate) (PHEMA) matrices. Responses of the sensing films to gaseous oxygen and dissolved oxygen were studied and the influence of the matrices on the sensing behaviors was investigated. Silica gel films had the highest fluorescence intensity ratio from deoxygenated to oxygenated environments and the fastest response time to oxygen. PHEMA films had no response to gaseous oxygen, but had greater sensitivity and a faster response time for dissolved oxygen than those of PS films. The influence of matrices on oxygen response, sensitivity and response time was discussed. The influence is most likely attributed to the oxygen diffusion abilities of the matrices. Since the probes were chemically immobilized in the matrices, no leaching of the probes was observed from the sensing films when applied in aqueous environment. One sensing film made from the PHEMA matrix was used to preliminarily monitor the oxygen consumption of Escherichia coli (E. coli) bacteria. E. coli cell density and antibiotics ampicillin concentration dependent oxygen consumption was observed, indicating the potential application of the oxygen sensing film for biological application. 相似文献
With the rapid deployment of smart meters, utilities and regulators across the globe are considering the deployment of time-varying rates for residential customers. Our analysis of the impact of several studies of time-varying rates from across the globe finds that much of the discrepancy in results across the studies goes away once demand response is expressed as a function of the peak to off-peak price ratio. 相似文献
Social media utilities have made it easier than ever to know about the range of online or offline social activities one could be engaging. On the upside, these social resources provide a multitude of opportunities for interaction; on the downside, they often broadcast more options than can be pursued, given practical restrictions and limited time. This dual nature of social media has driven popular interest in the concept of Fear of Missing Out – popularly referred to as FoMO. Defined as a pervasive apprehension that others might be having rewarding experiences from which one is absent, FoMO is characterized by the desire to stay continually connected with what others are doing. The present research presents three studies conducted to advance an empirically based understanding of the fear of missing out phenomenon. The first study collected a diverse international sample of participants in order to create a robust individual differences measure of FoMO, the Fear of Missing Out scale (FoMOs); this study is the first to operationalize the construct. Study 2 recruited a nationally representative cohort to investigate how demographic, motivational and well-being factors relate to FoMO. Study 3 examined the behavioral and emotional correlates of fear of missing out in a sample of young adults. Implications of the FoMOs measure and for the future study of FoMO are discussed. 相似文献
This study extends the research on message‐sensation value (MSV) by treating it as a dynamic stream of complex visual‐auditory information and arousing content (MSV‐d). Real‐time attentional and emotional responses to this dynamic stream during the PSA viewing process are indicated by psychophysiological measures. Dynamic models are used to systematically examine endogenous and exogenous influences on message processing to more accurately understand the effects of MSV‐d variables and individuals' sensation seeking tendencies during the processing of the PSAs. An important finding is that generally, increasing visual‐auditory complexity activates an approach tendency in those with high sensation‐seeking tendencies but activates an avoidance tendency in those with low sensation‐seeking tendencies, and this response pattern is moderated by arousing content. 相似文献
Ridge waveguide pseudomorphic InGaAs/GaAs/AlGaAs single-quantum-well lasers exhibiting record high quantum efficiencies and high output power densities (105 mW per facet from a 6 μm wide stripe) at a lasing wavelength of 980 nm are discussed that were fabricated from a graded index separate confinement heterostructure grown by molecular beam epitaxy. Life testing at an output power of 30 mW per uncoated facet reveals a slow gradual degradation during the initial 500 h of operation after which the operating characteristics of the lasers become stable. The emission wavelength, the high output power, and the fundamental lateral mode operation render these lasers suitable for pumping Er3+-doped fiber amplifiers 相似文献