Riboflavin-mediated delivery of a macromolecule into cultured human cells

The effects of perivascular nerve stimulation and phenylephrine on osmolyte release were studied in the intact perfused rat liver and isolated liver parenchymal cells (PC) and nonparenchymal cells. In the perfused liver, electrical stimulation of perivascular nerves (20 Hz/2 ms/20 V) led to a phentolamine-sensitive increase of cell hydration by 6.5% +/- 1.2% (n = 3) and a transient phentolamine-sensitive stimulation of taurine and inositol, but not betaine, release. These nerve effects were mimicked by phenylephrine, but not prostaglandin F2alpha, and were not affected by sodium nitroprusside (SNP) or ibuprofen. Nerve stimulation-induced taurine, but not inositol, release was inhibited by 4, 4'-di-isothiocyanatostilbene-2,2'-disulphonic acid (DIDS) (50 micromol/L). Single-cell fluorescence studies with isolated liver PC, Kupffer cells (KC), sinusoidal endothelial cells (SEC), and hepatic stellate cells (HSC) revealed that phenylephrine induced an increase in cytosolic free Ca2+ only in PC and HSC, but not in KC and SEC, whereas extracellular uridine triphosphate (UTP) produced Ca2+ transients/oscillations in all liver cell types studied. Phenylephrine had no effect on osmolyte release from isolated KC and SEC, but increased taurine (but not inositol) release from PC and inositol (but not taurine) efflux from HSC. The data suggest that: 1) liver cell hydration and-consecutively-osmolyte content are modulated by hepatic nerves via an alpha-adrenergic mechanism, which does not involve eicosanoids or hemodynamic changes; 2) that PC and HSC are the primary targets for nerve-dependent alpha-adrenergic activation, whereas 3) KC and SEC probably do not express alpha-adrenoceptors coupled to Ca2+ mobilization or osmolyte efflux.     

Challenges in Catalytic Manufacture of Renewable Pyrrolidinones from Fermentation Derived Succinate

Fermentation derived succinic acid ammonium salt is an ideal precursor for manufacture of renewable N-methyl pyrrolidinone (NMP) or 2-pyrrolidinone (2P) via heterogeneous catalysis. However, there are many challenges to making this a practical reality. Chief among the challenges is avoiding catalyst poisoning by fermentation by- and co-products. Battelle/Pacific Northwest National Laboratory have developed an effective technology strategy for this purpose. The technology is a combination of purely thermal processing, followed by simple catalytic hydrogenation that together avoids catalyst poisoning from fermentation impurities and provides high selectivity and yields of NMP or 2P.

     

"Have Fun While You Can,""You're Only as Old as You Feel," and "Don't Ever Get Old!": An Examination of Memorable Messages About Aging

Previous research has indicated memorable messages are important because they provide socializing functions by influencing cognitions and behaviors. This study examined the content, context, and structure of memorable messages about aging from the receiver's perspective. Message senders were older than receivers and tended to be female and family members. Senders usually were perceived to have benevolent motives. Messages did not tend to be rule-structured. Message content pertained to topics like the benefits of aging; aging as a natural, inevitable process; the need to enjoy life; and losses associated with aging. Message effects included viewing aging more positively, viewing aging more negatively, resolving to enjoy life or take better physical care of oneself, and changing relationships with others.     

Practice Variability and Transfer of Training: The Role of Self-Efficacy Generality.

Practice variability has been shown to enhance transfer of training. The purpose of the present study was to examine the role of self-efficacy generality as a motivational mechanism in explaining the relationship between practice variability and transfer. Undergraduate students (N = 82) were randomly assigned to 1 of 2 training conditions (constant or variable) for a computer decision-making task. Measures of self-efficacy (intensity and generality) and transfer (near and far) were assessed. The results provided support for some of the hypothesized relationships. Specifically, practice variability led to increased self-efficacy generality. Both self-efficacy intensity and generality influenced far transfer performance, although only self-efficacy generality served as a mediator between practice variability and far transfer. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Taking Care of Supply

A recurring theme for modern business is adaptability. The ability to exploit resources, skills and market position in new ways to increase returns on investment is paramount. Large companies in particular need to understand their internal and external supply chains to identify and evaluate new opportunities. BT has a history of developing and supplying all the services required by its end customers; but the world is changing rapidly, new types of player are emerging and BT now supplies its many services to many different types of customer — service providers, resellers and peers as well as end customers. There needs to be a way of understanding the implications of the different forms of customer/supplier relationship on the design and implementation of BT's systems.This paper presents a new set of patterns for businesses and their supply relationship. These patterns can be used to examine supply chains and the paper illustrates how these different supply relationships place different requirements on the operational support systems. Such patterns will be core to a flexible strategy within high performing, adaptable businesses.     

ABT-089 [2-methyl-3-(2-(S)-pyrrolidinylmethoxy)pyridine]: I. A potent and selective cholinergic channel modulator with neuroprotective properties

Lactate dehydrogenase from the malarial parasite Plasmodium falciparum has many amino acid residues that are unique compared to any other known lactate dehydrogenase. This includes residues that define the substrate and cofactor binding sites. Nevertheless, parasite lactate dehydrogenase exhibits high specificity for pyruvic acid, even more restricted than the specificity of human lactate dehydrogenases M4 and H4. Parasite lactate dehydrogenase exhibits high catalytic efficiency in the reduction of pyruvate, kcat/Km = 9.0 x 10(8) min(-1) M(-1). Parasite lactate dehydrogenase also exhibits similar cofactor specificity to the human isoforms in the oxidation of L-lactate with NAD+ and with a series of NAD+ analogs, suggesting a similar cofactor binding environment in spite of the numerous amino acid differences. Parasite lactate dehydrogenase exhibits an enhanced kcat with the analog 3-acetylpyridine adenine dinucleotide (APAD+) whereas the human isoforms exhibit a lower kcat. This differential response to APAD+ provides the kinetic basis for the enzyme-based detection of malarial parasites. A series of inhibitors structurally related to the natural product gossypol were shown to be competitive inhibitors of the binding of NADH. Slight changes in structure produced marked changes in selectivity of inhibition of lactate dehydrogenase. 7-p-Trifluoromethylbenzyl-8-deoxyhemigossylic acid inhibited parasite lactate dehydrogenase, Ki = 0.2 microM, which was 65- and 400-fold tighter binding compared to the M4 and H4 isoforms of human lactate dehydrogenase. The results suggest that the cofactor site of parasite lactate dehydrogenase may be a potential target for structure-based drug design.     

Reactions of lignin model compounds in ionic liquids

Lignin, a readily available form of biomass, is a potential source of renewable aromatic chemicals through catalytic conversion. Recent work has demonstrated that ionic liquids are excellent solvents for processing woody biomass and lignin. Seeking to exploit ionic liquids as media for depolymerization of lignin, we investigated reactions of lignin model compounds in these solvents. Using Brønsted acid catalysts in 1-ethyl-3-methylimidazolium triflate at moderate temperatures below 200 °C, we obtained up to 11.6% molar yield of the dealkylation product 2-methoxyphenol from the model compound 2-methoxy-4-(2-propenyl)phenol and cleaved 2-phenylethyl phenyl ether, a model for lignin ethers. Despite these successes, acid catalysis failed in dealkylation of the saturated-chain model compound 4-ethyl-2-methoxyphenol and did not produce monomeric products from organosolv lignin, demonstrating that further work is required to understand the complex chemistry of lignin depolymerization.     

Challenges in Catalytic Manufacture of Renewable Pyrrolidinones from Fermentation Derived Succinate

Fermentation derived succinic acid ammonium salt is an ideal precursor for manufacture of renewable N-methyl pyrrolidinone (NMP) or 2-pyrrolidinone (2P) via heterogeneous catalysis. However, there are many challenges to making this a practical reality. Chief among the challenges is avoiding catalyst poisoning by fermentation by- and co-products. Battelle/Pacific Northwest National Laboratory have developed an effective technology strategy for this purpose. The technology is a combination of purely thermal processing, followed by simple catalytic hydrogenation that together avoids catalyst poisoning from fermentation impurities and provides high selectivity and yields of NMP or 2P.     

Enterprise Modelling the Telecommunications Industry

The telecommunications industry is becoming both more co-operative and more competitive and this has dramatic consequences on the character of operational support. Operational activities make up the majority of telecommunications companies, and investment in these activities is huge. Dynamic markets and emerging new roles and supply chains stress the design of such operational systems and processes, some of which can trace their origins back to the monopolistic days of the past. This paper presents preparatory work in the search for new architectural tools to prepare operational support for the next millennium. The paper provides a definition for a value-adding enterprise and shows how conversation theory can help analyse the interaction of roles within an enterprise model. Such models can describe the interaction between responsibilities within enterprises and, in future, the required operational support systems, activities, data and processes.