Biomedical Ethics in the Soviet Union

*This is an abbreviated version of a paper presented first at a joint MIT-Harvard Faculty Seminar on the humanistic dimensions of Soviet Science on November 20, 1987, and then at the Western Michigan University Ethics Center on February 10, 1988. An expanded, fully documented version, under the title Soviet Biomedical Ethics will appear in a volume edited by Loren Graham, and tentatively entitled The Human Side of Soviet Science, Harvard University Press, 1989

Computers, Ethics and Business

When it comes to computers and computer-related activities, moral responsibility is in short supply. Our language often manifests the myth that computers are responsible and hence no one is to blame. This paper explores the idea that computer programmers are morally responsible for the consequences of their programming

Can Corporations Have Moral Responsibility?

Editor\u27s note: This paper was read at the eighth annual University of Dayton Philosophy Colloquium, held in 1979. The notion of collective moral responsibility has received relatively little treatment in the Anglo-American philosophical literature. This is surprising, given the increasingly widespread practice of ascribing moral responsibility to groups, peoples, and other collections of individuals. After World War II it was common for people to speak of the moral responsibility of the German people for Nazi atrocities; during the Viet Nam War many people accused America of immorality in carrying on an immoral war and using immoral tactics such as defoliation and napalm bombings; the whites in the United States have been said to be morally responsible for the plight of the blacks and responsible for making due reparation; and so on. There are many issues involved in the ascription of collective moral responsibility. In this paper I shall focus on collective responsibility as it pertains to corporations

Molecular mechanism of Gαi activation by non-GPCR proteins with a Gα-Binding and Activating motif

Heterotrimeric G proteins are quintessential signalling switches activated by nucleotide exchange on Gα. Although activation is predominantly carried out by G-protein-coupled receptors (GPCRs), non-receptor guanine-nucleotide exchange factors (GEFs) have emerged as critical signalling molecules and therapeutic targets. Here we characterize the molecular mechanism of G-protein activation by a family of non-receptor GEFs containing a Gα-binding and -activating (GBA) motif. We combine NMR spectroscopy, computational modelling and biochemistry to map changes in Gα caused by binding of GBA proteins with residue-level resolution. We find that the GBA motif binds to the SwitchII/α3 cleft of Gα and induces changes in the G-1/P-loop and G-2 boxes (involved in phosphate binding), but not in the G-4/G-5 boxes (guanine binding). Our findings reveal that G-protein-binding and activation mechanisms are fundamentally different between GBA proteins and GPCRs, and that GEF-mediated perturbation of nucleotide phosphate binding is sufficient for Gα activation

Supernova Remnants in the Fossil Starburst in M82

We report the discovery of ten compact H-alpha-bright sources in the post-starburst region northeast of the center of M82, ``M82 B.'' These objects have H alpha luminosities and sizes consistent with Type II supernova remnants (SNRs). They fall on the same H alpha surface brightness-diameter (Sigma-D) relation defined by SNRs in other nearby star-forming galaxies, with the M82 candidates lying preferentially at the small diameter end. These are the first candidates for optically-visible SNRs in M82 outside the heavily obscured central starburst within ~250 pc from the galactic center. If these sources are SNRs, they set an upper limit to the end of the starburst in region ``B2,'' about 500 pc from the galaxy's core, of ~50 Myr. Region ``B1,'' about 1000 pc from the core, lacks good SNR candidates and is evidently somewhat older. This suggests star formation in the galaxy has propagated inward toward the present-day intense starburst core.Comment: Re-submitted to AJ, referee's comments taken into account, 15 pages LaTeX preprint style, 4 postscript figures; full-resolution figures available from http://www.astro.virginia.edu/~rd7a/snrs/ Changes: minor textual changes and orientation/axes of Fig.

Interactions between neurokinin B and kisspeptin in mediating estrogen feedback in healthy women

CONTEXT: Kisspeptin and neurokinin B (NKB) are obligate for normal gonadotropin secretion, but their hierarchy is unexplored in normal women. OBJECTIVE: To investigate the interaction between kisspeptin and NKB on estrogen-regulated LH secretion. DESIGN: Women were treated with neurokinin-3 receptor (NK3R) antagonist followed by transdermal estradiol to induce LH secretion 48 hours later, with kisspeptin-10 or vehicle infusion during estrogen administration in a 2-way crossover study. SETTING: Clinical research facility. PATIENTS OR OTHER PARTICIPANTS: Healthy females with regular menses. INTERVENTION(S): NK3R antagonist AZD4901 40 mg twice daily orally was taken from cycle day 4–6 for 6 days (n = 10, with 10 no treatment controls). Transdermal estradiol patches (200 μg/d) were applied after 5 days of NK3R antagonist treatment. At 24-hour estradiol treatment, women were randomized to 7-hour kisspeptin-10 (4 μg/kg/h) or vehicle iv infusion, with the alternate infusion in a subsequent cycle. MAIN OUTCOME MEASURE(S): Plasma gonadotropin and estradiol secretion. RESULTS: After an initial suppression, LH secretion was increased 48 hours after estradiol treatment. Kisspeptin-10 increased LH secretion during the inhibitory phase, and LH remained elevated beyond the discontinuation of kisspeptin-10 infusion. NK3R antagonist decreased LH pulse frequency (0.5 ± 0.2 vs 0.7 ± 0.2 pulses/h, P < .05) and stimulated FSH response to kisspeptin-10 infusion (10.7 ± 11.0 vs 5.0 ± 3.6 IU/L, P < .05) with a nonsignificant rise in LH. The duration of LH response was blunted, with LH being lower at 48 hours (7.5 ± 4.8 vs 15.0 ± 11.4 IU/L, P < .05). CONCLUSIONS: These data demonstrate that NKB signaling regulates GnRH/LH secretion in normal women, and is predominantly proximal to kisspeptin in mediating estrogenic positive and negative feedback on LH secretion