The politics of conservative elites and the 'liberal media' argument

Recent evidence suggests that conservative elites' claims of a liberal media are having an impact upon public perceptions of news coverage. With this in mind, we examined two related questions in the context of the 1988, 1992, and 1996 presidential elections. First, what factors may be prompting conservative elites to make allegations of liberal media bias? Second, what factors may influence when news media report these criticisms during presidential campaigns? Findings suggest that these criticisms of news media are at least partly strategic and reflect a dynamic relationship between political elites and journalists during a presidential campaign.     

Statistical features of the avalanche multiplication build-up in semiconductors with different coefficients of impact ionization

The statistical fluctuations of the efficiency of the avalanche multiplication are studied for the Geiger- mode avalanche photodiodes. The resulting distribution function of the partial multiplication coefficients is characterized by an anomalously broad variance (on the order of the mean value). The expressions for the partial feedback coefficients are derived in terms of the mean gain, and the corresponding dependences on the over-voltage across the diode are calculated. An algorithm for the Monte-Carlo simulation of the avalanche process is presented, and the results of the statistical tests are compared with the theoretical dependence.     

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.     

Amide proton exchange measurements as a probe of the stability and dynamics of the N-terminal domain of the ribosomal protein L9: comparison with the intact protein

Amide H/D exchange rates have been measured for the N-terminal domain of the ribosomal protein L9, residues 1-56. The rates were measured at pD 3.91, 5.03, and 5.37. At pD 5.37, 18 amides exchange slowly enough to give reliable rate measurements. At pD 3.91, seven additional residues could be followed. The exchange is shown to occur by the EX2 mechanism for all conditions studied. The rates for the N-terminal domain are very similar to those previously measured for the corresponding region in the full-length protein (Lillemoen J et al., 1997, J Mol Biol 268:482-493). In particular, the rates for the residues that we have shown to exchange via global unfolding in the N-terminal domain agree within the experimental error with the rates measured by Hoffman and coworkers, suggesting that the structure of the domain is preserved in isolation and that the stability of the isolated domain is comparable to the stability of this domain in intact L9.     

Health economics and cost implications of anxiety and other mental disorders in the United States

BACKGROUND: Mental disorders impose a multi-billion dollar burden on the economy each year; translating the burden into economic terms is important to facilitate formulating policies about the use of resources. METHODS: For direct costs, data were obtained from national household interview and provider surveys; for morbidity costs, a timing model was used that measures the lifetime effect on current income of individuals with mental disorders, taking into account the timing of onset and the duration of these disorders, based on regression analysis of Epidemiologic Catchment Area study data. RESULTS: The total economic costs of mental disorders amounted to US$147.8 billion in 1990. Anxiety disorders are the most costly, amounting to $46.6 billion, or 31.5% of the total; schizophrenic disorders accounted for $32.5 billion, affective disorders for $30.4 billion, and other mental disorders for $38.4 billion. CONCLUSIONS: Mental illnesses, especially anxiety disorders, are costly to society. Although anxiety disorders have a higher prevalence than affective disorders and schizophrenia, use of medical care services is lowest for anxiety disorders. Anxiety disorders appear to be under-recognised and untreated even though treatment interventions have been shown to be effective and can be delivered in a cost-efficient manner.     

NIDA technical review: nitrite inhalants

Nitrite inhalants are commonly abused substances in the US and Europe. "Nitrite inhalants and AIDS" was a popular topic in the early 1980s when the cause of AIDS was not known. With the discovery of HIV, concern about nitrite use wained. However, nitrite inhalant use is associated with behavioral relapse and HIV transmission among gay men, with decreased lymphocyte counts and natural killer cell activity in laboratory studies, and remains a candidate "cofactor" in the pathogenesis of AIDS-related Karposi sarcoma. Discouraging nitrite use continues to be a worthwhile public health goal. Participants recommend specific research efforts.     

Epitope mapping using histidine-tagged protein fragments: application to Escherichia coli RNA polymerase sigma 70

The pathogenic Neisseria have exploited the processes of horizontal DNA transfer and genetic recombination as mechanisms for the generation of extensive protein variation and modulation of gene expression. Localized recombinations have been well documented in members of multigene families as have alterations in short repetitive sequences. Here we report an analysis of the chromosomal structure of a defined lineage of Neisseria gonorrhoeae strain MSl1 pilin variants. This study reveals the occurrence of large rearrangements, including the amplification of a 26 kb region and an inversion involving more than a third of the chromosome. Additionally, a restriction site polymorphism that correlates with pilin expression has been observed. These findings highlight the flexibility of the gonococcal genome.