Fluorescence Correlation Spectroscopy as a Quantitative Tool Applied to Drug Delivery Model Systems

The delivery of drugs to cells is a very active area of research. Drugs are commonly believed to ameliorate illnesses. The targeted, controlled and/or enhanced uptake of the drug into cells is facilitated by loading the drug into carrier vehicles (nanoparticles, e.g.. micelles).The distribution of a drug over the nanoparticles used to deliver the drug to the targeted cells is of vital importance. It makes a difference, whether all nanoparticles carry the same amount of drug or whether a little amount of the nanoparticles carries a high proportion of the drug material and most nanoparticles carry no material. This depends on the method used to load the drugs into the carriers. Furthermore, the absolute amount of drug present in the nanoparticles and the absolute number of nanoparticles loaded with drug molecules is very important, because "dosis venum facit" [Paracelsus]. We present an approach to resolve these issues by optical means.If the drug is fluorescent or labeled with a fluorescent label, fluorescence correlation spectroscopy (FCS) can be used to determine quantitative size distributions with a (confocal) microscope. In order to determine absolute concentrations the spatial dimensions of the confocal observation volume have to be known. These can be obtained from numerical simulations using vectorial diffraction theory. The theoretical results have been compared with experimental results from FCS using the calibration dye Rhodamine 6G. In a straightforward procedure the results were corrected for adsorption effects and excellent agreement to the theory was foun

Controlled, Stepwise Syntheses of Oligomers with Modified Quinoxaline Backbones

New oligomers based on quinoxaline units were successfully synthesized through multistep reactions using Wittig coupling, affording (E)-(quinoxalin-2-yl)ethene oligomers. Diverse quinoxaline-based phosphonium salts were designed and synthesized, enabling versatility and compatibility regarding the oligomer-building process. The characterization of the oligomers showed excellent stereoisomer specificity, i.e., a fully E-configurated conjugated π-system. The oligomers’ light absorption/emission profiles indicate potential properties for an application in materials science

MORE THAN FRIENDS: THE IMPACT OF SOCIAL MEDIA ON WORD OF MOUTH, BRAND LOYALTY AND PURCHASE INTENTIONS FOR INTERNATIONAL HOTELS

Purpose of the study: Increases in global travel have led to the internationalization of the hospitality industry. Though a number of applications of social media have been examined in the hospitality industry, few of them integrate key dimensions of fan pages into a measurement model in the same time, including interactivity (INT), engagement (ENG), trust (TRT), friendship (FRP), word-of-mouth (WOM) and purchase intention (PI). Methodology: Based on 408 valid fans from Facebook fan pages of 24 International hotels in Taiwan, the empirical results show that ENG, FRP, TRT, and WOM all act as partial mediators in their impact on post-purchase behaviors. Based on Taiwanese International hotels, this study attempts to explore why these owners want more than just a friend. Main findings: The empirical results show that ENG, FRP, TRT, and WOM all act as partial mediators in their impact on post-purchase behaviors. The study demonstrates the mechanisms behind utilizing social media to build solid long term potentially profitable relationships with hotel clientele. Originality/value: We propose and empirically investigate an integrated theoretical framework to more fully capture and describe the consumer’s behavior in the brand community. Our model of the social media process is informed by an “S-O-R” view from consumer behavior, where INT and ENG help create the situation which acts as a stimulus for FRP and TRT which in turn influence BL, WOM, and further PIs. Here, we see the pull force (website INT) as an influence on the brand-consumer relationship (i.e., FRP) through a push force (fan’s ENG). Together and along with the brand content they combine to create the consumer stimulus

Pregnancy Outcome with In Vitro Fertilization-Embryo Transfer According to Age in Women with Diminished Oocyte Reserve (DOR) using a Follicle Stimulating Hormone Receptor Up-Regulation Technique

Objective: About 18 years ago, one of the top IVF centers published a study and found that women with DOR did not have any live deliveries at any age in women with a day 3 serum FSH exceeding 18 mIU/mL. The failure to achieve a live delivery may have been related to the ovarian hyperstimulation regimen with possible down regulation of the FSH receptor needed to produce a key enzyme needed for successful implantation. The purpose of this 25-year retrospective review was to evaluate the efficacy of a specific type of mild stimulation referred to as the FSH receptor up-take technique on achieving live deliveries in women with extremely low egg reserve, and to determine the confounding effect of age. Materials and Methods: Inclusion criteria were as follows: 1) all ages up to 42.9 years, 2) the use of the FSH receptor up-regulation stimulation technique, 3) only 1 embryo was created which had \u3e4 blastomeres on day 3, 4) based on day 3 serum FSH (\u3e12 mIU/mL) and/or serum anti-mullerian hormone (AMH) levels (\u3c1ng/mL), there was evidence of DOR. Both clinical (ultrasound documented pregnancy at 8 weeks) and live delivered pregnancy rates were determined, 5) all cycles over a 25-year time were included. The same patient could be used more than once. The main tenets of the FSH receptor up-regulation technique are not only to use minimal FSH stimulation (usually no more than 75-150 IU FSH per day), but not to use any FSH if the serum level was \u3e12 mIU/mL. This allows the endogenous FSH to drive the follicular maturation, but when dropping levels of serum FSH is occurring related to rising serum estradiol (E2), one may add a mild dosage of FSH to either boost the 1 dominant follicle to full maturation, or to try to recruit more than one follicle. Ethinyl estradiol, 20 mcg, would be used for a short follicular phase or to restore down-regulated FSH receptors in women who appeared to be in overt menopause. Results: There were 1285 transfers of single day 3 embryos performed. A clinical and live delivered pregnancy rate was seen in 71 and 62 of 262 transfers (27% and 23.7%, respectively) in women \u3c age 35. A clinical and live delivered pregnancy was seen in 79 and 57 of 471 transfers (16.8% and 12.1%, respectively) in women aged 36-39. For women 40-42, clinical and live delivered pregnancies occurred in 71 and 34 of 552 transfers (12.9% and 6.2%, respectively). Overt ovarian failure (as defined by \u3e1 year of amenorrhea, no menses with progesterone treatment and withdrawal, serum E2/mL and serum FSH \u3e60 mIU/mL) was found in 334 of the 1285 transfers (26.0%). Conclusions: Using this FSH receptor up-regulation technique, live delivered pregnancy rates in women with severe DOR seem to be about twice as high in women ageoutcome

PREDICTIVE AI-BASED CHANNEL SOUNDING MECHANISM

Techniques are presented herein that support examining the channel state information (CSI) matrix that arises from a channel sounding and using the results of that examination to train a machine learning (ML)-based model that considers all of the available wireless parameters at each given measurement. Under the presented techniques, after sufficient training has been completed a CSI matrix may be predicted over short intervals (using, for example, a long short-term memory (LSTM) network) thus allowing a Wi-Fi access point (AP) to reduce the sounding frequency and, as a result, improve overall wireless performance

Simulating Quasi-Ballistic Transport in Si Nanotransistors

Electron transport in model Si nanotransistors is examined by numerical simulation using a hierarchy of simulation methods, from full Boltzmann, to hydrodynamic, energy transport, and drift-diffusion. The on-current of a MOSFET is shown to be limited by transport across a low-field region about one mean-free-path long and located at the beginning of the channel. Commonly used transport models based on simplified solutions of the Boltzmann equation are shown to fail under such conditions. The cause for this failure is related to the neglect of the carriers\u27 drift energy and to the collision-dominated assumptions typically used in the development of simplified transport models

Le sentiment d’appartenance à l’école : une analyse conceptuelle

Le sentiment d’appartenance à l’école est considéré comme un phénomène qui favorise la réussite scolaire et l’adaptation des jeunes à l’école. Malgré son importance, les études ne permettent pas d’en arriver à une représentation conceptuelle exhaustive de ce concept. Cet article vise à identifier les attributs définitionnels du sentiment d’appartenance à l’école dans le but de favoriser sa compréhension. La méthode conceptuelle privilégiée est celle de Walker et Avant (2011) qui comporte huit étapes distinctes permettant de mener un tel examen. La revue de la documentation a été menée par le biais de moteurs de recherche généralistes (p. ex. : Google, Google Scholar) et spécialisés (p. ex. : PsyInfo, Eric, Francis) en considérant les définitions en langues anglaise et française. En se basant sur l’analyse conceptuelle ayant été menée, quatre attributs définitionnels sont suggérés. L’élève doit : (1) ressentir une émotion positive à l’égard du milieu scolaire ; (2) entretenir des relations sociales positives avec les membres du milieu scolaire ; (3) s’impliquer activement dans les activités de la classe ou celles de l’école ; (4) percevoir une certaine synergie (harmonisation), voire une similarité, avec les membres de son groupe. En plus d’être abordés dans la perspective des principaux modèles théoriques en sciences de l’éducation qui tiennent compte du sentiment d’appartenance à l’école, ces attributs ont donné lieu à l’élaboration d’une nouvelle définition que nous présentons dans le présent article

Conservation and Variability of West Nile Virus Proteins

West Nile virus (WNV) has emerged globally as an increasingly important pathogen for humans and domestic animals. Studies of the evolutionary diversity of the virus over its known history will help to elucidate conserved sites, and characterize their correspondence to other pathogens and their relevance to the immune system. We describe a large-scale analysis of the entire WNV proteome, aimed at identifying and characterizing evolutionarily conserved amino acid sequences. This study, which used 2,746 WNV protein sequences collected from the NCBI GenPept database, focused on analysis of peptides of length 9 amino acids or more, which are immunologically relevant as potential T-cell epitopes. Entropy-based analysis of the diversity of WNV sequences, revealed the presence of numerous evolutionarily stable nonamer positions across the proteome (entropy value of ≤1). The representation (frequency) of nonamers variant to the predominant peptide at these stable positions was, generally, low (≤10% of the WNV sequences analyzed). Eighty-eight fragments of length 9–29 amino acids, representing ∼34% of the WNV polyprotein length, were identified to be identical and evolutionarily stable in all analyzed WNV sequences. Of the 88 completely conserved sequences, 67 are also present in other flaviviruses, and several have been associated with the functional and structural properties of viral proteins. Immunoinformatic analysis revealed that the majority (78/88) of conserved sequences are potentially immunogenic, while 44 contained experimentally confirmed human T-cell epitopes. This study identified a comprehensive catalogue of completely conserved WNV sequences, many of which are shared by other flaviviruses, and majority are potential epitopes. The complete conservation of these immunologically relevant sequences through the entire recorded WNV history suggests they will be valuable as components of peptide-specific vaccines or other therapeutic applications, for sequence-specific diagnosis of a wide-range of Flavivivirus infections, and for studies of homologous sequences among other flaviviruses