Publications

Prenol and isoprenol are promising advanced biofuels and serve as biosynthetic precursors for pharmaceuticals, fragrances, and other industrially relevant compounds. Despite engineering improvements that circumvent intermediate cytotoxicity and lower energy barriers, achieving high titer 'mevalonate (MVA)-derived' prenol has remained elusive. Difficulty in selective prenol production stems from the necessary isomerization of isopentenyl diphosphate (IPP) to dimethylallyl diphosphate (DMAPP) as well as the intrinsic toxicity of these diphosphate precursors. Here, the expression of specific isopentenyl monophosphate kinases with model-guided enzyme substitution of diphosphate isomerases and phosphatases enabled selective cycling of monophosphates and diphosphates, dramatically improving prenol titers and selectivity in Escherichia coli. Pairing this approach with the canonical MVA pathway resulted in 300 mg/L prenol at a 30:1 ratio with isoprenol. Further pairing with the "IPP-Bypass" pathway resulted in 526 mg/L prenol at a 72:1 ratio with isoprenol, the highest and purest MVA-derived prenol titer to date. Additionally, modifying this "IPP-Repass" for DMAPP production and coexpressing the prenyltransferase acPT1 yielded 48.3 mg/L of the potential therapeutic precursor drupanin from p-coumarate. These novel repass pathways establish a unique strategy for tuning diphosphate precursors to drive isoprenoid biosynthesis and prenylation reactions.

Osteoporotic patients treated with antiresorptive or anabolic agents experience an increase in bone mass and a reduction in incident fractures. However, the effects of these medications on bone quality and strength after a prolonged discontinuation of treatment are not known. We evaluated these effects in an osteoporotic rat model. Six-month-old ovariectomized (OVX) rats were treated with placebo, alendronate (ALN, 2 µg/kg), parathyroid hormone [PTH(1–34); 20 µg/kg], or raloxifene (RAL, 2 mg/kg) three times a week for 4 months and withdrawn from the treatments for 8 months. Treatment with ALN, PTH, and RAL increased the vertebral trabecular bone volume (BV/TV) by 47%, 53%, and 31%, with corresponding increases in vertebral compression load by 27%, 51%, and 31%, respectively (p < .001). The resulting bone strength was similar to that of the sham-OVX control group with ALN and RAL and higher (p < .001) with PTH treatment. After 4 months of withdrawal, bone turnover (BFR/BS) remained suppressed in the ALN group versus the OVX controls (p < .001). The vertebral strength was higher than in the OVX group only in ALN-treated group (p < .05), whereas only the PTH-treated animals showed a higher maximum load in tibial bending versus the OVX controls (p < .05). The vertebral BV/TV returned to the OVX group level in both the PTH and RAL groups 4 months after withdrawal but remained 25% higher than the OVX controls up to 8 months after withdrawal of ALN (p < .05). Interestingly, cortical bone mineral density increased only with PTH treatment (p < .05) but was not different among the experimental groups after withdrawal. At 8 months after treatment withdrawal, none of the treatment groups was different from the OVX control group for cortical or cancellous bone strength. In summary, both ALN and PTH maintained bone strength (maximum load) 4 months after discontinuation of treatment despite changes in bone mass and bone turnover; however, PTH maintained cortical bone strength, whereas ALN maintained cancellous bone strength. Additional studies on the long-term effects on bone strength after discontinuation and with combination of osteoporosis medications are needed to improve our treatment of osteoporosis. © 2011 American Society for Bone and Mineral Research.

There is increasing demand for 3D micro-scale time-resolved imaging of samples in realistic - and in many cases extreme environments. The data is used to understand material response, validate and refine computational models which, in turn, can be used to reduce development time for new materials and processes. Here we present the results of high temperature experiments carried out at the x-ray micro-tomography beamline 8.3.2 at the Advanced Light Source. The themes involve material failure and processing at temperatures up to 1750°C. The experimental configurations required to achieve the requisite conditions for imaging are described, with examples of ceramic matrix composites, spacecraft ablative heat shields and nuclear reactor core Gilsocarbon graphite.

“Beyond Li-ion” energy storage solutions based on ions such as Na, Mg, Ca, and Zn have attracted increasing attention due to growing concerns about the cost, resource availability, and safety of the currently dominant Li-ion batteries. One of the greatest challenges for beyond-Li systems, especially multivalent ones, is the lack of materials with high ionic mobility. In this study, we find that zircon-type YPO<sub>4</sub> presents a unique structural environment that enables superior conduction of multiple species including Na<sup>+</sup>, Ca<sup>2+</sup>, Mg<sup>2+</sup>, and Zn<sup>2+</sup>, even in the dilute carrier concentration regime. This highly unusual capability originates from one-dimensional (1D) percolating channels of adjacent, distorted octahedral sites, which results in a smoothly varying coordination environment and correspondingly low activation barriers. Low decomposition energy of multiple compositions of doped YPO<sub>4</sub>, where the carrier ions are introduced into the system along with subvalent doping into P sites, confirmed good stability and synthesizability. Among these compositions, we found Na<sub>0.0625</sub>YSi<sub>0.0625</sub>P<sub>0.9375</sub>O<sub>4</sub> exhibiting good Na<sup>+</sup> conductivity of 0.99 mS/cm at 300 K with an activation energy of 220 meV. Zircon-structured Na<sub>0.05</sub>YSi<sub>0.05</sub>P<sub>0.95</sub>O<sub>4</sub> was successfully synthesized; however, the highest density achieved (78%) was insufficient to conclusively establish its conductivity. Finally, we identify dopant–carrier association in doped YPO<sub>4</sub> as a key challenge for long-range diffusion in this structure family.

Abstract We present multiwavelength observations of the Swift short γ -ray burst GRB 231117A, localized to an underlying galaxy at redshift z = 0.257 at a small projected offset (∼2 kpc). We uncover long-lived X-ray Chandra X-ray Observatory and radio/millimeter (VLA, MeerKAT, and ALMA) afterglow emission, detected to ∼37 days and ∼20 days (rest frame), respectively. We measure a wide jet (∼10 <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" overflow="scroll"> <mml:mover> <mml:mrow> <mml:mo>.</mml:mo> </mml:mrow> <mml:mrow> <mml:mtext>°</mml:mtext> </mml:mrow> </mml:mover> </mml:math> 4) and relatively high circumburst density (∼0.07 cm −3 ) compared to the short GRB population. Our data cannot be easily fit with a standard forward shock model, but they are generally well fit with the incorporation of a refreshed forward shock and a reverse shock at &lt;1 day. We incorporate GRB 231117A into a larger sample of 132 X-ray detected events, 71 of which were radio-observed (17 cm-band detections), for a systematic study of the distributions of redshifts, jet and afterglow properties, galactocentric offsets, and local environments of events with and without detected radio afterglows. Compared to the entire short GRB population, the majority of radio-detected GRBs are at relatively low redshifts ( z &lt; 0.6) and have high circumburst densities (&gt;10 −2 cm −3 ), consistent with their smaller (&lt;8 kpc) projected galactocentric offsets. We additionally find that 70% of short GRBs with opening angle measurements were radio-detected, indicating the importance of radio afterglows in jet measurements, especially in the cases of wide (&gt;10°) jets where observational evidence of collimation may only be detectable at radio wavelengths. Owing to improved observing strategies and the emergence of sensitive radio facilities, the number of radio-detected short GRBs has quadrupled in the past decade.

Chronic nicotinic acid (NA) ingestion effectively lowers lipid levels, but adverse effects on glucose metabolism have been reported. Our goal was to investigate acute and chronic effects of NA on lipolysis and glucose metabolism in women. Healthy normolipidemic volunteers ( n = 5) were studied twice; four-day hospital stays were separated by 1 mo, during which time subjects took increasing doses of NA to 2 g/day (500 mg, 4 times). In the second study, 500 mg of NA was given at 0800. Rates of appearance (R a ) of free fatty acid (FFA), glycerol, and glucose were determined by isotope dilution (of [1,2,3,4- 13 C 4 ]palmitate, [2- 13 C 1 ]glycerol, and [U- 13 C 6 ]glucose). Mass isotopomer distribution analysis was used to measure gluconeogenesis and glycogenolysis. Fasting FFA concentrations ([FFA]), R a FFA, and R a glycerol were nonsignificantly elevated after 1 mo. Acute NA induced a significant reduction followed by a rebound overshoot of [FFA], R a FFA, and R a glycerol. Whole body fat oxidation fell initially and then increased back to basal levels; endogenous glucose production (EGP) increased in parallel with carbohydrate oxidation and then returned to basal values. The increased EGP was due entirely to increased glycogenolysis, not gluconeogenesis. We conclude that chronic effects of NA on FFA metabolism are complex (acute suppression followed by overshoot of R a FFA and [FFA] on top of a trend toward basal elevations), that responses after NA are consistent with operation of a glucose-fatty acid cycle in peripheral tissues, and that secondary effects on EGP were through changes in glycogenolysis, not gluconeogenesis.

We present broad-band multiwavelength observations of GRB 080310 at redshift z= 2.43. This burst was bright and long-lived, and unusual in having extensive optical and near-infrared (IR) follow-up during the prompt phase. Using these data we attempt to simultaneously model the gamma-ray, X-ray, optical and IR emission using a series of prompt pulses and an afterglow component. Initial attempts to extrapolate the high-energy model directly to lower energies for each pulse reveal that a spectral break is required between the optical regime and 0.3keV to avoid overpredicting the optical flux. We demonstrate that afterglow emission alone is insufficient to describe all morphology seen in the optical and IR data. Allowing the prompt component to dominate the early-time optical and IR and permitting each pulse to have an independent low-energy spectral indices we produce an alternative scenario which better describes the optical light curve. This, however, does not describe the spectral shape of GRB 080310 at early times. The fit statistics for the prompt- and afterglow-dominated models are nearly identical making it difficult to favour either. However one enduring result is that both models require a low-energy spectral index consistent with self-absorption for at least some of the pulses identified in the high-energy emission model.

Reinforcement learning (RL) algorithms involve the deep nesting of highly irregular computation patterns, each of which typically exhibits opportunities for distributed computation. We argue for distributing RL components in a composable way by adapting algorithms for top-down hierarchical control, thereby encapsulating parallelism and resource requirements within short-running compute tasks. We demonstrate the benefits of this principle through RLlib: a library that provides scalable software primitives for RL. These primitives enable a broad range of algorithms to be implemented with high performance, scalability, and substantial code reuse. RLlib is available at this https URL.