32 research outputs found
Observations of the High Redshift Universe
(Abridged) In these lectures aimed for non-specialists, I review progress in
understanding how galaxies form and evolve. Both the star formation history and
assembly of stellar mass can be empirically traced from redshifts z~6 to the
present, but how the various distant populations inter-relate and how stellar
assembly is regulated by feedback and environmental processes remains unclear.
I also discuss how these studies are being extended to locate and characterize
the earlier sources beyond z~6. Did early star-forming galaxies contribute
significantly to the reionization process and over what period did this occur?
Neither theory nor observations are well-developed in this frontier topic but
the first results presented here provide important guidance on how we will use
more powerful future facilities.Comment: To appear in `First Light in Universe', Saas-Fee Advanced Course 36,
Swiss Soc. Astrophys. Astron. in press. 115 pages, 64 figures (see
http://www.astro.caltech.edu/~rse/saas-fee.pdf for hi-res figs.) For lecture
ppt files see
http://obswww.unige.ch/saas-fee/preannouncement/course_pres/overview_f.htm
Secular trends in the survival of HIV-infected homosexual men in Amsterdam and Vancouver estimated from a death-included CD4-staged Markov model
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Macromolecular Antiproliferative Agents Featuring Dicarboxylato-Chelated Platinum
Cancerous diseases, together with cardiac afflictions, account for the predominant causes of death among the adult population of the Western world. The classical platinum drugs, with cisplatin as their parent, have established themselves for years as leading components in the oncologist’s arsenal of antitumor agents. As with most other antineoplastic drugs, however, incisive pharmacological deficiencies, notably excessive systemic toxicity and induction of drug resistance, have severely curtailed their overall efficaciousness. With the objective of overcoming these counterproductive deficiencies, the technique of polymer-drug conjugation, representing an advanced modality of drug delivery, has been developed in recent years to high standards worldwide. In a drug conjugate, water-soluble macromolecular carrier constructs designed in compliance with stringent pharmacological specifications are covalently, yet bioreversibly, interconnected with the bioactive agent. As a macromolecule following a pharmacokinetic pathway different from that of non-polymeric compounds, the conjugate acts as a pro-drug favorably transporting the agent through the various body compartments to, and into, the target cell, where the agent is enzymatically or hydrolytically separated from the carrier for its biological action. In the authors’ laboratories the conjugation strategy has been adopted as the primary tool for drug efficacy enhancement. The present paper describes a special type of platinum complex carrier-bound via dicarboxymetal chelation, synthesized from carboxyl-functionalized polyamide-type carriers by platination with trans-1,2-diaminocyclohexanediaquaplatinum(II) dinitrate. In a series of in vitro tests antiproliferative activities have been determined against several human cancer cell lines. Whereas no improvements are observed in tests against a colorectal cancer, outstanding findings of the screening program include a 10- to 100-fold increase in cell-killing performance of the conjugates relative to the (non-polymeric) cisplatin standard against the HeLa adenocarcinoma, and distinctly reduced resistance factors (again, relative to cisplatin) in tests against the A2780 and A2780-cis pair of ovarian cell lines. These findings augur well for future developments of this class of platinum drugs