Analogues of capsaicin with agonist activity as novel analgesic agents: structure-activity studies. 4. Potent, orally active analgesics

Structural features of three regions of the capsaicin molecule necessary for agonist properties were delineated by a previously reported modular approach. These in vitro agonist effects were shown to correlate with analgesic potency in rodent models. Combination of optimal structural features from each of these regions of the capsaicin molecule have led to highly potent agonists (eg., 1b). Evaluation in vivo established that 1b had analgesic properties but poor oral activity, short duration of action, and excitatory side effects which precluded further development of this compound. Preliminary metabolism studies had shown that the phenol moiety of 1b was rapidly glucuronidated in vivo, providing a possible explanation for the poor pharmacokinetic profile. Subsequent specific modification of the phenol group led to compounds 2a-j, which retained in vitro potency. The in vivo profiles of two representatives of this series, 2a,h, were much improved over the "parent" phenol series, and they are candidates for development as analgesic agents.     

Roald Amundsen--a study of personality

Roald Amundsen is the most famous of the Norwegian polar explorers. His ancestors came from a group of islands south-east of the Oslofjord. From being fishermen and sailors, they progressed to becoming captains and shipowners in the course of two generations. Amundsen's father, Jens, stayed at sea until his ship went down with all the crew. Roald was 14 years of age at the time, the youngest of four competing brothers. Jens had left the close-knit local family community before that, and bought a flat in the capital, Oslo, so that his sons could get a better education. Roald's mother wanted him to study medicine. He did as she wished for a time, but was not at all interested. When his mother died, he abruptly left the university and went to sea, which had been the tradition in his family for decades. As a young boy he was an admirer of Sir John Franklin and his explorers of the Northwest Passage. Fridtjof Nansen became his ideal. The biographies about Roald Amundsen are very diverging--some hold him a hero, others reflect a strongly critical attitude. Here, the author tries to define his personality and places him firmly within the narcissistic domain. His tendency to seek the company of married women, but to take immediate flight when they really became interested reflects an Oedipus complex from before puberty. The tragic death of his father, the sea captain, may have been a supposition; puberty can be seen as a period of coping with ambivalence towards an earlier idealized father. His genius combined ambitious goals with a sharp eye for details as regards the equipment used in his expeditions. In his travels in the Arctic and the Antartic he was driven forward by the energy of the nation. His heroic death, trying to save his earlier "enemy", Nobile, was probably caused by an urge for self-destruction.     

CHL1 encodes a component of the low-affinity nitrate uptake system in Arabidopsis and shows cell type-specific expression in roots

The Arabidopsis CHL1 (AtNRT1) gene confers sensitivity to the herbicide chlorate and encodes a nitrate-regulated nitrate transporter. However, how CHL1 participates in nitrate uptake in plants is not yet clear. In this study, we examined the in vivo function of CHL1 with in vivo uptake measurements and in situ hybridization experiments. Under most conditions tested, the amount of nitrate uptake by a chl1 deletion mutant was found to be significantly less than that of the wild type. This uptake deficiency was reversed when a CHL1 cDNA clone driven by the cauliflower mosaic virus 35S promoter was expressed in transgenic chl1 plants. Furthermore, tissue-specific expression patterns showed that near the root tip, CHL1 mRNA is found primarily in the epidermis, but further from the root tip, the mRNA is found in the cortex or endodermis. These results are consistent with the involvement of CHL1 in nitrate uptake at different stages of root cell development. A functional analysis in Xenopus oocytes indicated that CHL1 is a low-affinity nitrate transporter with a K(m) value of approximately 8.5 mM for nitrate. This finding is consistent with the chlorate resistance phenotype of chl1 mutants. However, these results do not fit the current model of a single, constitutive component for the low-affinity uptake system. To reconcile this discrepancy and the complex uptake behavior observed, we propose a "two-gene" model for the low-affinity nitrate uptake system of Arabidopsis.     

Individual,social, and organizational contexts for active knowledge sharing in communities of practice

Firms that have implemented knowledge management initiatives are now interested in nurturing voluntary knowledge sharing organizations, called communities of practice (CoPs). Adopting the Triandis model on attitude formation, we identified and validated a set of organizational factors that was anticipated to have effects on knowledge sharing by CoP members such as perceived consequences, affect, social factors and facilitating conditions. One hundred and seventy-nine members from 70 CoPs of a large multinational electronics firm participated in this survey. Based on the PLS analysis, perceived consequences, affect, social factors, and facilitating conditions were found to significantly affect knowledge sharing in CoPs.     

Leveraging online communities in fostering adaptive schools

There has long been a call for schools to prepare students for the twenty-first century where skills and dispositions differ significantly from much of what has historically characterized formal education. The knowledge based economy calls for policy and pedagogical efforts that would transform schools. Schools are to foster communities of learners. This paper suggests that para-communities may be points of leverage in the fostering of adaptive schools. A critical analysis is done on the differences between para-communities (such as online communities) and schools; and an argument is made that they each serve differing goals and should be left distinct because they achieve different societal and economic demands.     

Differential effects of elevated potassium ion concentration and of theophylline on growth hormone release by rat adenohypophyses in vitro

The effects of 27 mM K+ and of 6.7 mM theophylline on the release of growth hormone (GH) by rat hemipituitaries in vitro were investigated using bioassay (rat tibia test) and radioimmunoassay (RIA). Both agents markedly increased the release of immunoreactive GH. High K+ also promoted the release of bioactive GH but to a much lesser degree than RIA-GH. Theophylline did not consistently affect the release of bioassay-detectable GH. The results suggest that these agents promote massive release of a form of immunoreactive GH (possibly "immature") that has little or no activity in the bioassay. Theophylline is relatively more effective in this regard than is elevated K+.     

Using online collaboration applications for group assignments: The interplay between design and human characteristics

In recent years, educators and students are increasingly employing online collaboration applications such as Google Docs™ and PBWorks™ for group projects and assignments. Yet, the effectiveness of these emerging technologies has not been rigorously examined. Anchoring upon and informed by the existing literature, two design characteristics – sociability and visibility, and two human characteristics – gender and age, are focused on, which are salient in online collaboration applications. A field experiment was conducted to examine the direct and moderating effects of design and human characteristics on learning outcomes. The research found that sociability improved process satisfaction and positive social environment while visibility enhanced academic performance and solution satisfaction of learners. Males had higher solution satisfaction while older learners had higher academic performance. Moderating effects were also found. Both theoretical and practical implications are drawn. In particular, a rubric for online collaboration application selection for academic performance is conceived. This study provides empirical support for online collaboration application effectiveness in education which will augur well for future adoption, use and evolution.     

Material properties and growth control of undoped and Sn-doped In2O3 thin films prepared by using ion beam technologies

Undoped (IO) and Sn-doped In₂O₃ (ITO) films have been deposited on glass and polymer substrates by an advanced ion beam technologies including ion-assisted deposition (IAD), hybrid ion beam, ion beam sputter deposition (IBSD), and ion-assisted reaction (IAR). Physical and chemical properties of the oxide films and adhesion between films and substrates were improved significantly by these technologies. By using the IAD method, non-stoichiometry and microstructure of the films were controlled by changing assisted oxygen ion energy and arrival ratio of assisted oxygen ion to evaporated atoms. Relationships between structural and electrical properties in ITO films on glass substrates were intensively investigated by using the IBSD method with changing ion energy, reactive gas environment, and substrate temperature. Smooth-surface ITO films (R_rms ≤ 1 nm and R_p-v ≤ 10 nm) for organic light-emitting diodes were developed with a combination of deposition conditions with controlling microstructure of a seed layer on glass. IAR surface treatment enormously enhanced the adhesion of oxide films to polymer substrate. The different dependence of IO and ITO films' properties on the experimental parameters, such as ion energy and oxygen gas environment, will be intensively discussed.     

Advances in Vapor Pressure Modeling for Electronic Packaging

Two advanced techniques have been developed for modeling vapor pressure within the plastic IC packages during solder reflow. The first involves the extension of the "wetness" technique to delamination along multimaterial interface and during dynamic solder reflow. Despite its simplicity, this technique is capable of offering reliable and accurate prediction for packages with high flexural rigidity. For packages with low flexural rigidity, the new "decoupling" technique that integrates thermodynamics, moisture diffusion, and structural analysis into a unified procedure has been shown to be more useful. The rigorous technique has been validated on both leadframe-based as well as laminate-based packages. With high accuracy and computational efficiency, these dynamic modeling tools will be valuable for optimization of package construction, materials, and solder reflow profile against popcorn cracking for both SnPb and Pb-free solders     

Ultraflat indium tin oxide films prepared by ion beam sputtering

Indium tin oxide (ITO) films with a smooth surface (root-mean-square roughness; R_rms=0.40 nm) were made using a combination of the deposition conditions in the ion beam-sputtering method. Sheet resistance was 13.8 Ω/sq for a 150-nm-thick film grown at 150 °C. Oxygen was fed into the growth chamber during film growth up to 15 nm, after which, the oxygen was turned off throughout the rest of the deposition. The surface of the films became smooth with the addition of ambient oxygen but electrical resistance increased. In films grown at 150 °C with no oxygen present, a rough surface (R_rms=2.1 nm) and low sheet resistance (14.4 Ω/sq) were observed. A flat surface (R_rms=0.5 nm) with high sheet resistance (41 Ω/sq) was obtained in the films grown with ambient oxygen throughout the film growth. Surface morphology and microstructure of the films were determined by the deposition conditions at the beginning of the growth. Therefore, fabrication of ITO films with a smooth surface and high electrical conductivity was possible by combining experimental conditions.