Studies Toward the Total Synthesis of Antibiotic 593A

In 1970 art article was published in the Journal of Antibiotics in which the isolation of a substance from the south African soil microorganism Streptomyces griseolutus designated 593A (NSC-135758) was reported. It was reported to inhibit the growth of human tumors in the chick embryo. Arison and Beck in 1973 proposed the structure to be 3,6-bis-(5-chloro-2 -piperidyl-)-2 ,5-piperizinedione based on spectral data. In the ensuing years a number of further studies were made on the activity of 593A, It was found to be active against a number of solid tumors, several variants of leukemia, and in selectively inhibiting DNA synthesis. A possible mode of operation was suggested in which the Antibiotic would form a bis-aziridine derivative which acts as an alkylating agent

Gambling and public health: we need policy action to prevent harm

No abstract available

Approach to the Synthesis of the Acyltetramic Acid Antibiotic Bu-2313

An approach to the synthesis of the bicyclononane portion of the 3-acyltetramic acid antibiotic Bu-2313 is presented. The highly unstable α-ketoaldehyde obtained by Swern oxidation of the diol 30 was allowed to condense with the unreactive α-ketophosphoranylidene 18 affording the enedione 31. The silyl ether was cleaved and the hydroxyl caused to add to the enedione in a five-exo fashion to form the tetrahydrofuran. The combination of functional groups necessary for ketal formation was investigated showing that the system does not form the desired ketal in most circumstances (Table I). Given the correct functional group array, it was shown that the ketalization is more favorable with the stereochemistry of the natural product.</p

Framing a public health approach to gambling harms in Wales: Challenges and opportunities

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Bayesian analysis of polarization measurements

A detailed and formal account of polarization measurements using Bayesian analysis is given based on the assumption of gaussian error for the Stokes parameters. This analysis is crucial for the measurement of the polarization degree and angle at very low (and very high) signal-to-noise. The treatment serves as a framework for customized analysis of data based on a particular prior suited to the experiment.Comment: 15 page

Gambling as a public health issue in Wales

No abstract available

Nocturnal thoracoabdominal asynchrony in house dust mite-sensitive nonhuman primates

Nocturnal bronchoconstriction is a common symptom of asthma in humans, but is poorly documented in animal models. Thoracoabdominal asynchrony (TAA) is a noninvasive clinical indication of airway obstruction. In this study, respiratory inductive plethysmography (RIP) was used to document nocturnal TAA in house dust mite (HDM)-sensitive Cynomolgus macaques. Dynamic compliance (Cdyn) and lung resistance (RL) measured in anesthetized animals at rest and following exposure to HDM allergen, methacholine, and albuterol were highly correlated with three RIP parameters associated with TAA, ie, phase angle of the rib cage and abdomen waveforms (PhAng), baseline effort phase relation (eBPRL) and effort phase relation (ePhRL). Twenty-one allergic subjects were challenged with HDM early in the morning, and eBPRL and ePhRL were monitored for 20 hours after provocation. Fifteen of the allergic subjects exhibited gradual increases in eBPRL and ePhRL between midnight and 6 am, with peak activity at 4 am. However, as in humans, this nocturnal response was highly variable both between subjects and within subjects over time. The results document that TAA in this nonhuman primate model of asthma is highly correlated with Cdyn and RL, and demonstrate that animals exhibiting acute responses to allergen exposure during the day also exhibit nocturnal TAA