Resting metabolic rate and lung function in wild offshore common bottlenose dolphins, Tursiops truncatus, near Bermuda

© The Author(s), 2018. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Frontiers in Physiology 9 (2018): 886, doi:10.3389/fphys.2018.00886.Diving mammals have evolved a suite of physiological adaptations to manage respiratory gases during extended breath-hold dives. To test the hypothesis that offshore bottlenose dolphins have evolved physiological adaptations to improve their ability for extended deep dives and as protection for lung barotrauma, we investigated the lung function and respiratory physiology of four wild common bottlenose dolphins (Tursiops truncatus) near the island of Bermuda. We measured blood hematocrit (Hct, %), resting metabolic rate (RMR, l O2 ⋅ min-1), tidal volume (VT, l), respiratory frequency (fR, breaths ⋅ min-1), respiratory flow (l ⋅ min-1), and dynamic lung compliance (CL, l ⋅ cmH2O-1) in air and in water, and compared measurements with published results from coastal, shallow-diving dolphins. We found that offshore dolphins had greater Hct (56 ± 2%) compared to shallow-diving bottlenose dolphins (range: 30–49%), thus resulting in a greater O2 storage capacity and longer aerobic diving duration. Contrary to our hypothesis, the specific CL (sCL, 0.30 ± 0.12 cmH2O-1) was not different between populations. Neither the mass-specific RMR (3.0 ± 1.7 ml O2 ⋅ min-1 ⋅ kg-1) nor VT (23.0 ± 3.7 ml ⋅ kg-1) were different from coastal ecotype bottlenose dolphins, both in the wild and under managed care, suggesting that deep-diving dolphins do not have metabolic or respiratory adaptations that differ from the shallow-diving ecotypes. The lack of respiratory adaptations for deep diving further support the recently developed hypothesis that gas management in cetaceans is not entirely passive but governed by alteration in the ventilation-perfusion matching, which allows for selective gas exchange to protect against diving related problems such as decompression sickness.Funding for this project was provided by the Office of Naval Research (ONR YIP Award No. N000141410563, and Dolphin Quest, Inc. FHJ was supported by the Office of Naval Research (Award No. N00014-1410410) and an AIAS-COFUND fellowship from Aarhus Institute of Advanced Studies under the FP7 program of the EU (Agreement No. 609033)

Power-to-Gas Implementation for a Polygeneration System in Southwestern Ontario

Canada has stockpiles of waste petroleum coke, a high carbon waste product leftover from oil production with little positive market value. A polygeneration process is proposed which implements “power-to-gas” technology, through the use of electrolysis and surplus grid electricity, to use waste petroleum coke and biomass to create a carbon monoxide-rich stream after gasification, which is then converted into a portfolio of value-added products with the addition of hydrogen. A model implementing mixed-integer linear programming integrates power-to-gas technology and AspenPlus simulates the polygeneration process. The downstream production rates are selected using particle swarm optimization. When comparing 100% electrolysis vs. 100% steam reforming as a source of hydrogen production, electrolysis provides a larger net present value due to the carbon pricing introduced in Canada and the cost reduction from removal of the air separation unit by using the oxygen from the electrolysers. The optimal percent of hydrogen produced from electrolysis is about 82% with a hydrogen input of 7600 kg/h. The maximum net present value is $332 M when over 75$203 M when the dimethyl ether is capped at 50% production. The polygeneration plant is an example of green technology used to environmentally process Canada’s petroleum coke

Deep diving by offshore bottlenose dolphins (Tursiops spp.)

We used satellite-linked tags to evaluate dive behavior in offshore bottlenose dolphins (Tursiops spp.) near the island of Bermuda. The data provide evidence that bottlenose dolphins commonly perform both long (&amp;gt;272 s) and deep (&amp;gt;199 m) dives, with the deepest and longest dives being to 1,000 m and 826 s (13.8 min), respectively. The data show a relationship between dive duration and dive depth for dives longer than about 272 s. There was a diurnal pattern to dive behavior, with most dives deeper than 50 m being performed at night; deep diving began at sunset and varied throughout the night. We used the cumulative frequency of dive duration to estimate a behavioral aerobic dive limit (bADL) of around 560-666 s (9.3-11.1 min) in adult dolphins in this population. Dives exceeding the bADL spent significantly longer time in the upper-most 50 m following a dive as compared with dives less than the bADL. We conclude that the offshore ecotype off Bermuda, unlike the shallow-diving near-shore bottlenose dolphin, is a deep-diving ecotype, and may provide a useful animal model to study extreme diving behavior and adaptations.Funding Agencies|Office of Naval Research (ONR YIP award) [N00014-14-1-0563]; Dolphin Quest Inc.</p

Discovery of BMS-641988, a Novel Androgen Receptor Antagonist for the Treatment of Prostate Cancer

BMS-641988 (<b>23</b>) is a novel, nonsteroidal androgen receptor antagonist designed for the treatment of prostate cancer. The compound has high binding affinity for the AR and acts as a functional antagonist <i>in vitro</i>. BMS-641988 is efficacious in multiple human prostate cancer xenograft models, including CWR22-BMSLD1 where it displays superior efficacy relative to bicalutamide. Based on its promising preclinical profile, BMS-641988 was selected for clinical development

Discovery of the Selective CYP17A1 Lyase Inhibitor BMS-351 for the Treatment of Prostate Cancer

Efforts to identify a potent, reversible, nonsteroidal CYP17A1 lyase inhibitor with good selectivity over CYP17A1 hydroxylase and CYPs 11B1 and 21A2 for the treatment of castration-resistant prostate cancer (CRPC) culminated in the discovery of BMS-351 (compound <b>18</b>), a pyridyl biaryl benzimidazole with an excellent <i>in vivo</i> profile. Biological evaluation of BMS-351 at a dose of 1.5 mg in castrated cynomolgus monkeys revealed a remarkable reduction in testosterone levels with minimal glucocorticoid and mineralcorticoid perturbation. Based on a favorable profile, BMS-351 was selected as a candidate for further preclinical evaluation

Discovery of Clinical Candidate BMS-906024: A Potent Pan-Notch Inhibitor for the Treatment of Leukemia and Solid Tumors

Structure–activity relationships in a series of (2-oxo-1,4-benzodiazepin-3-yl)-succinamides identified highly potent inhibitors of γ-secretase mediated signaling of Notch1/2/3/4 receptors. On the basis of its robust in vivo efficacy at tolerated doses in Notch driven leukemia and solid tumor xenograft models, <b>12</b> (BMS-906024) was selected as a candidate for clinical evaluation