Oxidation of unsaturated fatty acids with ruthenium and osmium tetroxide

The oxidation of the alkali metal salts of oleic and undecylenic acid with ruthenium and osmium tetroxides is reported. The oxidants are used in catalytic amounts in conjunction with an excess of the in-expensive cooxidant sodium hypochlorite. Ruthenium tetroxide cleaves the carbon-carbon double bond of potassium oleate, to give pelargonic and gives sebacic acid. With osmium tetroxide, hydroxylation of the double bond of potassium oleate gives a 95% yield oferythro-9,10-dihydroxystearic acid. The osmium tetroxide oxidation of sodium undecylenate results in the formation of 10,11-dihydroxyundecanoic acid and the cleavage product sebacic acid in varying yields.     

Ion-dipole interactions between adsorbed CO and support cations in Pt/K-LTL

The adsorption of carbon monoxide on a non-acidic Pt/K-LTL catalyst has been studied by diffuse reflectance and transmission IR spectroscopy. The CO spectrum is strongly dependent on the experimental conditions. Adsorption on the small Pt clusters in the presence of water gives linear-CO bands between 2060 and 1990 cm^–1 and a bridging-CO band around 1800 cm^–1. In the absence of water, the linear bands are red shifted to about 1940 and 1720 cm^–1, respectively. The frequency shift is attributed to an ion-dipole interaction between adsorbed CO and support cations. The ion-dipole interaction is screened by the adsorbed water leading to a smaller red shift in the CO stretching frequency.     

Clustering research fields for macro-strategic analysis: A comparative specialization approach

The goal of this article is to show that it is possible to construct an index to measure a country's relative specialization in different scientific fields in a way which is both reliable and relevant for macro-strategic analysis. We will call this index a Revealed Scientific Advantages Index. The technical problem to be discussed is one of aggregation: how can we be sure that an index calculated for a small number of relatively large fields does not mask significant policy needs synthetic measures which are easy to interpret. We will show that the Revealed Scientific Advantages approach offers the possibility of building them. The study itself is based on figures obtained through an exploitation of the INIST/CNRS PASCAL database classification of science. 107 sub-fields of this classification were initially used to determine the areas of specialization for 11 countries (revealed national advantages). Clustering techniques were then used to aggregate this data and 13 specific fields were identified. The science policy information produced during the study concerned these 13 fields. It proved to be both easily understandable and relevant for macro-strategic analysis.     

Apoptosis and its role in human disease

In a landmark paper published over two decades ago, Kerr et al. proposed the term apoptosis "for a hitherto little recognized mechanism of controlled cell deletion, which appears to play a complementary but opposite role to mitosis in the regulation of animal cell populations". In the ensuing years, this natural cell death process was studied at the basic science level, primarily with a view to understanding its roles in cancer and in the development and maintenance of the immune system. More recently, however, evidence has suggested a role for the failure of normal apoptosis control in many of the major diseases of the industrialized world. Though complex, apoptosis appears amenable to therapeutic intervention. The range of modern pharmaceutical strategies available to treat such disregulated gene-directed processes offers promise for advances in the control of cancer, immune system and neurodegenerative disorders, heart disease, and perhaps even the aging process itself.     

Log-linear allometry of fetal craniofacial growth in Down's syndrome

Trisomy 21 develops as a result of nondisjunction of two homologous chromosomes during either the first or second meiotic division. One of the more important consequences of these genetic alterations is the predictable, although variable disturbance in the architecture of the craniofacial region [1]. Postnatal craniofacial morphology has been extensively studied in Down's syndrome (DS). However, little information is available on human prenatal development of the head and face in such patients. The time at which changes in craniofacial phenotype first emerge in Down's syndrome fetuses and at which physical growth begins to diverge from normal is unknown. To explore these questions, we compared prenatal craniofacial growth in 50 Down's syndrome fetuses with that of 555 fetuses judged to be "typical for body weight and age" using the method of log-linear allometry [2].     

Autoimmunity, immunodeficiency and mucosal infections: chronic intestinal inflammation as a sensitive indicator of immunoregulatory defects in response to normal luminal microflora

Despite the fact that target antigens and the genetic basis of several autoimmune diseases are now better understood, the initial events leading to a loss of tolerance towards self-components remain unknown. One of the most attractive explanations for autoimmune phenomena involves various infections as possible natural events capable of initiating the process in genetically predisposed individuals. The most accepted explanation of how infection causes autoimmunity is based on the concept of "molecular mimicry" (similarity between the epitopes of an autoantigen and the epitopes in the environmental antigen). Infectious stimuli may also participate in the development of autoimmunity by inducing an increased expression of stress proteins (hsp), chaperones and transplantation antigens, which leads to abnormal processing and presentation of self antigens. Superantigens are considered to be one of the most effective bacterial components to induce inflammatory reactions and to take part in the development and course of autoimmune mechanisms. It has long been known that defects in the host defense mechanism render the individual susceptible to infections caused by certain microorganisms. Impaired exclusion of microbial antigens can lead to chronic immunological activation which can affect the tolerance to self components. Defects in certain components of the immune system are associated with a higher risk of a development of autoimmune disease. The use of animal models for the studies of human diseases with immunological pathogenesis has provided new insights into the influence of immunoregulatory factors and the lymphocyte subsets involved in the development of disease. One of the most striking conclusion arising from work with genetically engineered immunodeficient mouse models is the existence of a high level of redundancy of the components of the immune system. However, when genes encoding molecules involved in T cell immunoregulatory functions are deleted, spontaneous chronic inflammation of the gut mucosa (similar to human inflammatory bowel disease) develops. Surprisingly, when such immunocompromised animals were placed into germfree environment, intestinal inflammation did not develop. Impairment of the mucosal immune response to the normal bacterial flora has been proposed to play a crucial role in the pathogenesis of chronic intestinal inflammation. The use of immunodeficient models colonized with defined microflora for the analysis of immune reactivity will shed light on the mode of action of different immunologically important molecules responsible for the delicate balance between luminal commensals, nonspecific and specific components of the mucosal immune system.     

Endogenous Neighborhood Selection and the Attainment of Cooperation in a Spatial Prisoner’s Dilemma Game

There is a large literature in economics and elsewhere on the emergence and evolution of cooperation in the repeated Prisoner’s Dilemma. Recently this literature has expanded to include games in a setting where agents play only with local neighbors in a specified geography. In this paper we explore how the ability of agents to move and choose new locations and new neighbors influences the emergence of cooperation. First, we explore the dynamics of cooperation by investigating agent strategies that yield Markov transition probabilities. We show how different agent strategies yield different Markov chains which generate different asymptotic behaviors in regard to the attainment of cooperation. Second, we investigate how agent movement affects the attainment of cooperation in various networks using agent-based simulations. We show how network structure and density can affect cooperation with and without agent movement.     

Urbanisation and Shallow Groundwater: Predicting Changes in Catchment Hydrological Responses

The impact of urbanisation on catchment hydrological response was investigated by using a process-based coupled surface water–groundwater model (MODHMS). The modelling estimated likely changes in river discharge as a result of land-use change in the Southern River catchment in Western Australia, underlined by a highly transmissive aquifer, has permeable soils and a shallow watertable. A significant increase in total annual discharge was predicted as a result of urbanisation area with the runoff coefficient rising from 0.01 to more than 0.40. In contrast with urban areas elsewhere, these changes were mainly due to a shift in the subsurface water balance, leading to significant reduction in evaporative losses from the soil profile and shallow watertable after urbanisation (from nearly 80 % of infiltration to less than 20 %). The infiltration of roof and road runoff and establishment of subsurface drainage adopted in local construction practice leads to higher groundwater recharge rates and subsequently groundwater discharge to the urban drainage network. Urban density and groundwater abstraction for urban irrigation most strongly influence the urbanisation impact on catchment fluxes. The results shows that urban development leads to a production of ‘harvestable’ water; and depending on local needs, this water could be used for public and private water supply or to improve environmental flows.     

Comparison of the chronic toxicity of piroxantrone, losoxantrone and doxorubicin in spontaneously hypertensive rats

We have determined the time course, the spatial spread in brain tissue, and the intracellular distribution of biotin- and fluorescein-labeled phosphorothioate oligodeoxynucleotides (ODNs) following single injections into the rat striatum or the lateral ventricle. These time and space parameters were correlated with the ability of c-fos phosphorothioate antisense ODNs to suppress the induction of Fos protein by cocaine. A rapid and dose-dependent tissue penetration of labeled ODNs was observed following either intrastriatal or intraventricular injections of a constant sample volume. Inspection of tissue sections by confocal microscopy uncovered a distinct change in the intracellular disposition of labeled ODNs during the 24 h post-injection period. At 1, 6 and 12 h, the vast majority of the fluorescent signal was confined to the interstitial spaces throughout the zone penetrated by ODNs. Neuronal nuclei displayed faint labeling along the outer portion of the nucleus at 1 and 6 h post-injection. At these time-points, ODNs were not detected in the cytoplasm. By 16 h, ODNs were barely detectable in the extracellular space and absent from neuronal nuclei. Instead, ODNs were seen in large cytoplasmic granules of neurons throughout the tissue zone penetrated by the ODNs. Experiments with intrastriatal injections of antisense ODNs to c-fos mRNA revealed Fos suppression between 3 and 12 h, but not at 16 and 24 h. This combined analysis has revealed that (1) restricted tissue penetration by ODNs limits their antisense effects on protein expression, and (2) depletion of extracellular ODNs and sequestration of c-fos antisense ODNs into large intracellular granules coincides with the loss of their biological activity.     

The antitumour activity of the prodrug N-L-leucyl-doxorubicin and its parent compound doxorubicin in human tumour xenografts

The antitumour activity of the investigational agent N-L-leucyl-doxorubicin (Leu-DOX) was compared with that of doxorubicin (DOX) in human tumour xenografts growing subcutaneously in athymic nude mice. Leu-DOX was developed as a prodrug of DOX, and may be converted into the clinically active parent compound by hydrolytic enzymes present in or on tumour cells. It has been suggested that a better therapeutic index with a reduced cardiac toxicity and higher efficacy might be obtained. Both compounds were administered intravenously weekly for 2 weeks, each at maximum tolerated doses of 8 mg/kg and 28 mg/kg for DOX and Leu-DOX, respectively. The panel of xenografts represented three different tumour types. Leu-DOX showed antitumour activity, defined as tumour growth inhibition > 50% and specific growth delay > 1.0, in 10 of the 16 tumours, including two of five breast, five of seven small cell and three of four non-small cell lung carcinomas. In comparison, DOX was active in one breast, four small cell lung and two lung adenocarcinoma xenografts. In all the DOX sensitive lung tumours, Leu-DOX showed higher efficacy than the parent compound. Based on the results of the present study, and since phase I clinical trials with Leu-DOX have already been performed, phase II clinical evaluation of Leu-DOX in patients with breast and lung cancer is recommended.