Visfatin in pregnancy: proposed mechanism of peptide delivery.

Visfatin is a newly identified 52 kD adipocytokine that appears to have insulinomimetic properties. We examined visfatin expression in visceral fat from lean and pregnant women. Visfatin gene expression was seven times higher in omental fat of pregnant women than in lean women. Both immunohistochemistry and immunoblot confirmed that visfatin protein was much higher in pregnant women than in nonpregnant women. However, serum visfatin was 20.8 +/- 7.7 ng/ml (n = 7) in lean women as compared to only a slight increase to 40.3 ng/ml in pregnant women (n = 4). We measured visfatin mRNA content of human placenta and found that placenta expresses high levels of visfatin mRNA and protein. At a concentration of 2 nM, visfatin and insulin produced nearly identical increase in glucose transport. The discrepancy between the elevated visfatin expression and tissue visfatin compared to only a small increase in serum visfatin is a matter of controversy. The data on serum visfatin concentrations are replete with contradictory data. Taken together, we suggest that visfatin is not a hormone. Instead, we propose that visfatin acts in either a paracrine or autocrine mode. This hypothesis would explain what various laboratories have found widely discrepant values for serum visfatin. Since visfatin potently and efficaciously induced glucose transport in a cell culture model, any hypothetical role for visfatin in pregnancy should include the possibility that it may play a role in maternal/fetal glucose metabolism or distribution and that it may do so by acting locally.

The principles of tomorrow's university.

In the 21st Century, research is increasingly data- and computation-driven. Researchers, funders, and the larger community today emphasize the traits of openness and reproducibility. In March 2017, 13 mostly early-career research leaders who are building their careers around these traits came together with ten university leaders (presidents, vice presidents, and vice provosts), representatives from four funding agencies, and eleven organizers and other stakeholders in an NIH- and NSF-funded one-day, invitation-only workshop titled "Imagining Tomorrow's University." Workshop attendees were charged with launching a new dialog around open research - the current status, opportunities for advancement, and challenges that limit sharing. The workshop examined how the internet-enabled research world has changed, and how universities need to change to adapt commensurately, aiming to understand how universities can and should make themselves competitive and attract the best students, staff, and faculty in this new world. During the workshop, the participants re-imagined scholarship, education, and institutions for an open, networked era, to uncover new opportunities for universities to create value and serve society. They expressed the results of these deliberations as a set of 22 principles of tomorrow's university across six areas: credit and attribution, communities, outreach and engagement, education, preservation and reproducibility, and technologies. Activities that follow on from workshop results take one of three forms. First, since the workshop, a number of workshop authors have further developed and published their white papers to make their reflections and recommendations more concrete. These authors are also conducting efforts to implement these ideas, and to make changes in the university system.  Second, we plan to organise a follow-up workshop that focuses on how these principles could be implemented. Third, we believe that the outcomes of this workshop support and are connected with recent theoretical work on the position and future of open knowledge institutions.

Estrogens induce visfatin expression in 3T3-L1 cells.

Visfatin is a 56 kDa protein that is overexpressed in pregnant women. Like insulin, 2 nM visfatin induced GLUT 4 translocation from the cytosolic fraction to the membrane in 3T3-L1 cells. We have previously reported that visfatin induces glucose uptake into 3T3-L1 cells. These two actions define visfatin as an insulinomimetic. Three estrogens are elevated in pregnancy. Estradiol, the predominant estrogen, estriol, produced by the fetal liver and the pro-estrogen progesterone are all higher during pregnancy than in nonparous women. 3T3-L1 cells were treated with 150 ng/ml estriol, 16 ng/ml estradiol or 190 ng/ml progesterone to reflect the circulating concentrations of these steroids during pregnancy. Estriol treatment produced a 2.5-fold increase in visfatin gene expression. Estradiol and progesterone had small but insignificant effects on visfatin gene expression. In a second experiment, cells were treated with a combination of all three steroids together at the same concentrations listed above. The combination treatment produced a 13-fold increase in visfatin gene expression. These data suggest that the estriol, estradiol and progesterone exert a synergistic effect on visfatin gene expression. Taken together these data suggest that visfatin may play a physiological role during pregnancy. Since visfatin potently and efficaciously induced GLUT 4 translocation in a cell culture model, any hypothetical role for visfatin in pregnancy should include the possibility that it may play a role in maternal/fetal glucose metabolism or distribution. Two possibilities present: either maternal visfatin is overexpressed as a protective response in the pregnant female to compensate for the insulin resistance that often accompanies pregnancy or the excess visfatin is a compensatory response to ensure adequate glucose delivery to the growing fetus.

Accurate evolution of orbiting binary black holes.

We present a detailed analysis of binary black hole evolutions in the last orbit and demonstrate consistent and convergent results for the trajectories of the individual bodies. The gauge choice can significantly affect the overall accuracy of the evolution. It is possible to reconcile certain gauge-dependent discrepancies by examining the convergence limit. We illustrate these results using an initial data set recently evolved by Brügmann et al. [Phys. Rev. Lett. 92, 211101 (2004)10.1103/PhysRevLett.92.211101]. For our highest resolution and most accurate gauge, we estimate the duration of this data set's last orbit to be approximately 59MADM.