Micellar modification of drug stability: analysis of the effect of hexadecyltrimethylammonium halides on the rate of degradation of cephaclor

The intra- and intermolecular rates of degradation of cephaclor were determined with and without hexadecyltrimethylammonium bromide (CTABr). Micellar-derived spectral shifts were used to measure the association of the ionic forms as well as to determine the effect of CTABr on the apparent acid dissociation constant of the antibiotic. The rate of degradation of cephaclor increased with detergent and was salt sensitive. Micellar effects were analyzed quantitatively within the frame-work of the speudophase ion exchange model. All experimental data were fitted to this model which was used to predict the combined effects of pH and detergent concentration. Micelles increased the rate of OH- attack on cephaclor; most of the effect was due to the concentration of reagents in the micellar pseudophase. The intramolecular degradation was catalyzed 25-fold by micelles, and a working hypothesis to rationalize this effect is proposed. The results demonstrate that quantitative analysis can be utilized to assess and predict effects of detergents on drug stability.

Different levels of policy change: A comparison between the public discussion on social security in Sweden and in Finland

The deep economic recession that hit Sweden and Finland at the beginning of the 90s, and the fall in public revenues and rapidly growing public debts that followed on it, triggered a development of cutbacks and restructuring measures which has resulted in a scientific debate over what this has meant for these countries’ systems of social policy, traditionally resting on the Nordic welfare state paradigm. In this connection, questions of to what extent changes made can be ascribed mainly to the economic constraints posed by the recession at all, or rather, to other more long-term societal trends or phenomena, including globalisation, European integration and/or ideational or ideological shifts among influential (elite) groups, have often been touched upon. Applying an ideas-centred approach, this paper attempts to contribute to the knowledge on the reasoning of influential elite societal groups in social policy issues before, during and after the 90’s recession, by empirically analysing their statements on social security made in the press. A distinction is made between three different levels of proposed policy changes, reaching from minor alterations of single programs to changes of the policy paradigm. Results show that the 1990s did not only mean the emergence of suggestions for minor cutbacks in and alterations of prevailing programmes. The share of suggestions implying de facto a (further) departure from the basic features of the social security system also showed that the model was under continuous pressure throughout the 90s. However, many of the changes suggested were not justified by any clear references to a policy paradigm in either country (or not justified at all). Instead, references to “purely” structural justifications did become more common over time. In this respect, as regards social security, our results cannot confirm the fairly popular notion among many researchers of a clearly ideological attack on the welfare state. However, it remains uncertain whether and to what extent the increased proportion of references to “structural realities” in the 90s should be interpreted as an indication of a change in the idea of what the welfare state is and what the goals behind it are. Results further show that the patterns of the discussion in the two countries studied bore a remarkable resemblance at a general level, whereas there are indications of differences in the driving forces behind suggestions for similar reforms in these two countries.

A Call for Systematic Research on Solute Carriers

Solute carrier (SLC) membrane transport proteins control essential physiological functions, including nutrient uptake, ion transport, and waste removal. SLCs interact with several important drugs, and a quarter of the more than 400 SLC genes are associated with human diseases. Yet, compared to other gene families of similar stature, SLCs are relatively understudied. The time is right for a systematic attack on SLC structure, specificity, and function, taking into account kinship and expression, as well as the dependencies that arise from the common metabolic space.

Plankton biomass in the Mamala Basin (Oahu Island, Hawaii Islands) under antropogenic influence in August-September of 2002-2004

Anthropogenic impact on biomass of coastal plankton communities caused by submerged disposal of urban sewage waters (dumping) was studied. Observations were carried out in August-September of 2002-2004 in the Mamala Bay (Oahu Island, Hawaii Islands) using satellite and straight sea measurements. An analysis of variability of integral indicators of the water column determined on the basis of on-board measurements allowed us to divide them into two groups: elements most sensitive to pollution (heterotrophic bacteria (H-Bact), phototrophic cyanobacteria Synechococcus spp. (SYN), and chlorophyll a (CHLa)) and elements that manifested episodic positive dependence on inflow of polluted waters (heterotrophic unicellular eukaryotes, small unicellular algae, phototrophic green bacteria Prochlorococcus spp., as well as total biomass of microplankton). It was shown that submerged waste water disposal in the region of the diffuser of the dumping device led to insignificant (aver. 1.2-1.4 times) local increase in integral biomass of H-Bact, SYN, and in concentration of CHLa. Similar but sharper (aver. 1.5-2.1 times) increase in these parameters was found in water layers with maximal biomasses. Possible pathways of disposed waters (under the pycnocline, at its upper boundary, and in the entire mixed layer) were analyzed on the basis of studying vertical displacement of biomasses of H-Bact, SYN, and prochlorophytes. Possibility of using optical anomalies distinguished from satellite data as markers of anthropogenic eutrophication caused by dumping was confirmed. Application of such markers depends on water transparency and on shapes of curves of vertical distribution of autotrophic organisms.

Potency of Michael reaction acceptors as inducers of enzymes that protect against carcinogenesis depends on their reactivity with sulfhydryl groups

Induction of phase 2 enzymes and elevations of glutathione are major and sufficient strategies for protecting mammals and their cells against the toxic and carcinogenic effects of electrophiles and reactive forms of oxygen. Inducers belong to nine chemical classes and have few common properties except for their ability to modify sulfhydryl groups by oxidation, reduction, or alkylation. Much evidence suggests that the cellular “sensor” molecule that recognizes the inducers and signals the enhanced transcription of phase 2 genes does so by virtue of unique and highly reactive sulfhydryl functions that recognize and covalently react with the inducers. Benzylidene-alkanones and -cycloalkanones are Michael reaction acceptors whose inducer potency is profoundly increased by the presence of ortho- (but not other) hydroxyl substituent(s) on the aromatic ring(s). This enhancement correlates with more rapid reactivity of the ortho-hydroxylated derivatives with model sulfhydryl compounds. Proton NMR spectroscopy provides no evidence for increased electrophilicity of the β-vinyl carbons (the presumed site of nucleophilic attack) on the hydroxylated inducers. Surprisingly, these ortho-hydroxyl groups display a propensity for extensive intermolecular hydrogen bond formation, which may raise the reactivity and facilitate addition of mercaptans, thereby raising inducer potencies.

Crystallographic evidence for the action of potassium, thallium, and lithium ions on fructose-1,6-bisphosphatase.

Fructose-1,6-bisphosphatase (Fru-1,6-Pase; D-fructose-1,6-bisphosphate 1-phosphohydrolase, EC 3.1.3.11) requires two divalent metal ions to hydrolyze alpha-D-fructose 1,6-bisphosphate. Although not required for catalysis, monovalent cations modify the enzyme activity; K+ and Tl+ ions are activators, whereas Li+ ions are inhibitors. Their mechanisms of action are still unknown. We report here crystallographic structures of pig kidney Fru-1,6-Pase complexed with K+, Tl+, or both Tl+ and Li+. In the T form Fru-1,6-Pase complexed with the substrate analogue 2,5-anhydro-D-glucitol 1,6-bisphosphate (AhG-1,6-P2) and Tl+ or K+ ions, three Tl+ or K+ binding sites are found. Site 1 is defined by Glu-97, Asp-118, Asp-121, Glu-280, and a 1-phosphate oxygen of AhG-1,6-P2; site 2 is defined by Glu-97, Glu-98, Asp-118, and Leu-120. Finally, site 3 is defined by Arg-276, Glu-280, and the 1-phosphate group of AhG-1,6-P2. The Tl+ or K+ ions at sites 1 and 2 are very close to the positions previously identified for the divalent metal ions. Site 3 is specific to K+ or Tl+. In the divalent metal ion complexes, site 3 is occupied by the guanidinium group of Arg-276. These observations suggest that Tl+ or K+ ions can substitute for Arg-276 in the active site and polarize the 1-phosphate group, thus facilitating nucleophilic attack on the phosphorus center. In the T form complexed with both Tl+ and Li+ ions, Li+ replaces Tl+ at metal site 1. Inhibition by lithium very likely occurs as it binds to this site, thus retarding turnover or phosphate release. The present study provides a structural basis for a similar mechanism of inhibition for inositol monophosphatase, one of the potential targets of lithium ions in the treatment of manic depression.

Blurring the lines : how Japanese American internment camps re-defined art and religion's relationship

After the Japanese bombed Pearl Harbor during WWII, anyone of Japanese descent living on the West Coast was placed in internment camps scattered throughout the country. Life inside the camps included many different activities to make life as normal as possible. This study will focus on two intersecting day-to-day activities in particular, the practice of religion within the camps, as well as the creation of art. Art created in the camps was influenced by multiple religious traditions. An analysis of artworks created by professional and amateur artists, interviews and an examination of existing scholarship demonstrates that internment camps created a unique environment for the creation of art. The values of internees reflected the seamless coexistence of Christianity, Buddhism and Shinto in internment camp art.

Boston 2000: harbor nodes, modes & links

Shows transportation network in and around the harbor.

Summary of the action of the ... regular session of the Wisconsin Legislature on some of the more important questions coming before it /

Description based on: 1941.

Report to the Legislature of the State of Hawaii

Mode of access: Internet.

A letter to the editor of the letters : on the spirit of patriotism, the idea of a patriot-king, and the state of parties, &c. : Occasioned by the editor's advertisement.

Verso of half title (p. [2]) and t.p. (p. [4]) blank.

Modern Shakespearean criticism : as exhibited in a letter, which was published in The Stratford-on-Avon Herald, of Friday, the 9th November, 1888, and which is here separately reprinted for the consideration of those who may be interested in the character of Shakespearean controversy.

In manuscript on verso of fly-leaf: "Only ten copies printed, J.G. Bishop."

Stories by foreign authors.

Spanish: [v.10] The tall woman, by P.A. de Alarcón. -- The white butterfly, by J. Selgas. -- The organist, by G.A. Becquer. -- Moors and Christians, by P.A. de Alarcón. -- Bread cast upon the waters, by Fernan Caballero.

Levels and probable origin of predatory scarring on humpback whales (Megaptera novaeangliae) in east Australian waters

To investigate the incidence of non-lethal predation in Southern Hemisphere whales, more than 3400 fluke-identification photographs from resight histories of 1436 east Australian humpback whales were examined for evidence of predatory markings. Photographs were obtained from 1984 to 1996 at various locations along the east coast of Australia, from northern Queensland to southern New South Wales. Photographs were classified in terms of the level and type of scarring. The possible predator and whether the markings appeared fresh were also noted. In all, 17% of identified east Australian humpbacks possessed some form of predatory scarring, 57% of which was minor and 43% major. Almost all predatory scarring was consistent with that inflicted by killer whales. Only three whales demonstrated an increase in the level of predatory scarring after their first sightings. Two incidents of fresh scarring were recorded, and one fatal killer whale attack on a humpback whale calf was directly observed. The overall level of predatory scarring found in this study is comparable to those found in studies for Northern Hemisphere humpback whales. The low incidence of adult whales showing their first sign of predatory scarring after their initial sighting, and the small number possessing recent scarring, support the idea that east Australian humpback whales experience most predatory attacks early in life.

Conflicting obligations: Pufendorf, Leibniz and Barbeyrac on civil authority

Barbeyrac's republication of and commentary on Leibniz' attack on Pufendorf's natural-law doctrine is often seen as symptomatic of the failure of all three early moderns to solve a particular moral-philosophical problem: that of the relationship between civil authority and morality. Making use of the first English translation of Barbeyrac's work, this article departs from the usual view by arguing that here we are confronted by three conflicting constructions of civil obligation, arising not from the common intellectual terrain of moral philosophy, but from divergent religious and political cultures. If this approach makes the three constructions less susceptible to theoretical reconciliation, then it opens them to a more revealing historical investigation, in terms of the particular religious and political circumstances in which they arose, and which they were designed to address. The result is that these early modern struggles over the nature of civil obligation confront us again as unfinished historical business.