Publications

1. The effects of purified diets containing 70% glucose or 70% fructose on the activation state of hepatic pyruvate dehydrogenase (PDHa), activity of mitochondrial PDH kinase, plasma triacylglycerols (TG) and hepatic lipogenesis de novo in rats were measured. 2. Plasma TG were significantly increased in the fructose-fed compared with the glucose-fed group (125 +/- 45 mg/dl versus 57 +/- 19 mg/dl; P less than 0.002) after 3-5 weeks on the diet despite less daily food intake. 3. Hepatic PDHa in fructose-fed rats was 144% of the value in glucose-fed rats (15.4 +/- 1.2% versus 10.7 +/- 0.5%; P less than 0.002), whereas cardiac muscle PDHa was not different (45.5 +/- 6.6% versus 41.0 +/- 7.8%). 4. Intrinsic hepatic PDH kinase activity was decreased to 34% of glucose-fed values by fructose feeding (-k = 3.56 +/- 0.39 versus 10.41 +/- 1.85 min-1; P less than 0.005). 5. The fractional contribution to very-low-density-lipoprotein palmitate from hepatic lipogenesis de novo, measured by a stable-isotope mass-spectrometric method, was 10.49 +/- 2.42% (n = 8) in fructose-fed rats versus 5.55 +/- 1.38% (n = 9) in glucose-fed rats (P less than 0.05), and 2.66 +/- 2.39% (n = 3) in chow-fed rats (P less than 0.05 versus fructose-fed group). The absolute contribution to circulating TG from lipogenesis de novo was also significantly higher in the fructose-fed than in the glucose-fed group (14.9 +/- 5.1 mg/dl versus 2.9 +/- 0.6 mg/dl; P less than 0.05) 6. Portal insulin concentrations were significantly higher in the fructose-fed rats (206 +/- 49 mu-units/ml versus 81 +/- 15 mu-units/ml; P less than 0.05). 7. In conclusion, dietary fructose appears to have a specific activating effect on hepatic PDH, mediated at least in part by inhibition of PDH kinase. These results are consistent with increased flux through hepatic PDH and synthesis of new fat, not just increased re-esterification of non-esterified fatty acids.

view Abstract Citations (30) References (17) Co-Reads Similar Papers Volume Content Graphics Metrics Export Citation NASA/ADS A Gravitational Lens Candidate Discovered with the Hubble Space Telescope Maoz, Dan ; Bahcall, John N. ; Schneider, Donald P. ; Doxsey, Rodger ; Bahcall, Neta A. ; Filippenko, Alexei V. ; Goss, W. M. ; Lahav, Ofer ; Yanny, Brian Abstract We report evidence for gravitational lensing of the high-redshift (z = 3.8) quasar 1208+101, observed as part of the Snapshot Survey with the Hubble Space Telescope Planetary Camera. An HST V image taken on gyroscopes resolves the quasar into three point-source components, with the two fainter images having separations of 0.1" and 0.5" from the central bright component. A radio observation of the quasar with the Very Large Array at 2 cm shows that, like most quasars of this redshift, 1208+101 is radio-quiet. Based on positional information alone, the probability that the observed optical components are chance superpositions of Galactic stars is small, but not negligible. Analysis of a combined ground-based spectrum of all three components, using the relative brightnesses from the HST image, supports the lensing hypothesis. If all the components are lensed images of the quasar, the observed configuration cannot be reproduced by simple lens models. Future HST observations can test the lensing hypothesis for 1208+101. Publication: The Astrophysical Journal Pub Date: February 1992 DOI: 10.1086/186278 Bibcode: 1992ApJ...386L...1M Keywords: Gravitational Lenses; Hubble Space Telescope; Quasars; Radio Astronomy; Red Shift; Very Large Array (Vla); Milky Way Galaxy; Point Spread Functions; Radio Telescopes; Astrophysics; COSMOLOGY: GRAVITATIONAL LENSING; GALAXIES: QUASARS: INDIVIDUAL ALPHANUMERIC: 1208; 101 full text sources ADS | data products SIMBAD (5) NED (4) MAST (1) ESA (1)

New methods for the general asymmetric synthesis of sulfonimidamides are of great interest due to their applications in medicinal chemistry, agrochemical discovery, and academic research. We report a palladium-catalyzed cross-coupling method for the enantioselective aryl-carbonylation of sulfonimidamides. Using data science techniques, a virtual library of calculated bisphosphine ligand descriptors was used to guide reaction optimization by effectively sampling the catalyst chemical space. The optimized conditions identified using this approach provided the desired product in excellent yield and enantioselectivity. As the next step, a data science-driven strategy was also used to explore a diverse set of aryl and heteroaryl iodides, providing key information about the scope and limitations of the method. Furthermore, we tested a range of racemic sulfonimidamides for compatibility of this coupling partner. The developed method offers a general and efficient strategy for accessing enantioenriched sulfonimidamides, which should facilitate their application in industrial and academic settings.

Large-scale atomistic simulations are essential to bridge computational materials and chemistry to realistic materials and drug discovery applications. In the past few years, rapid developments of machine learning interatomic potentials (MLIPs) have offered a solution to scale up quantum mechanical calculations. Parallelizing these interatomic potentials across multiple devices poses a challenging, but promising approach to further extending simulation scales to real-world applications. In this work, we present DistMLIP, an efficient distributed inference platform for MLIPs based on zero-redundancy, graph-level parallelization. In contrast to conventional space-partitioning parallelization, DistMLIP enables efficient MLIP parallelization through graph partitioning, allowing multi-device inference on flexible MLIP model architectures like multi-layer graph neural networks. DistMLIP presents an easy-to-use, flexible, plug-in interface that enables distributed inference of pre-existing MLIPs. We demonstrate DistMLIP on four widely used and state-of-the-art MLIPs: CHGNet, MACE, TensorNet, and eSEN. We show that existing foundational potentials can perform near-million-atom calculations at the scale of a few seconds on 8 GPUs with DistMLIP.

Large language models (LLMs) have rapidly improved text embeddings for a growing array of natural-language processing tasks. However, their opaqueness and proliferation into scientific domains such as neuroscience have created a growing need for interpretability. Here, we ask whether we can obtain interpretable embeddings through LLM prompting. We introduce question-answering embeddings (QA-Emb), embeddings where each feature represents an answer to a yes/no question asked to an LLM. Training QA-Emb reduces to selecting a set of underlying questions rather than learning model weights. We use QA-Emb to flexibly generate interpretable models for predicting fMRI voxel responses to language stimuli. QA-Emb significantly outperforms an established interpretable baseline, and does so while requiring very few questions. This paves the way towards building flexible feature spaces that can concretize and evaluate our understanding of semantic brain representations. We additionally find that QA-Emb can be effectively approximated with an efficient model, and we explore broader applications in simple NLP tasks.

Treatment with acetyl-CoA carboxylase inhibitors (ACCi) in nonalcoholic steatohepatitis (NASH) may increase plasma triglycerides (TGs), with variable changes in apoB concentrations. ACC is rate limiting in de novo lipogenesis and regulates fatty acid oxidation, making it an attractive therapeutic target in NASH. Our objectives were to determine the effects of the ACCi, firsocostat, on production rates of plasma LDL-apoB in NASH and the effects of combined therapy with fenofibrate. Metabolic labeling with heavy water and tandem mass spectrometric analysis of LDL-apoB enrichments was performed in 16 NASH patients treated with firsocostat for 12 weeks and in 29 NASH subjects treated with firsocostat and fenofibrate for 12 weeks. In NASH on firsocostat, plasma TG increased significantly by 17% from baseline to week 12 (P = 0.0056). Significant increases were also observed in LDL-apoB fractional replacement rate (baseline to week 12: 31 ± 20.2 to 46 ± 22.6%/day, P = 0.03) and absolute synthesis rate (ASR) (30.4-45.2 mg/dl/day, P = 0.016) but not plasma apoB concentrations. The effect of firsocostat on LDL-apoB ASR was restricted to patients with cirrhosis (21.0 ± 9.6 at baseline and 44.2 ± 17 mg/dl/day at week 12, P = 0.002, N = 8); noncirrhotic patients did not change (39.8 ± 20.8 and 46.3 ± 14.8 mg/dl/day, respectively, P = 0.51, N = 8). Combination treatment with fenofibrate and firsocostat prevented increases in plasma TG, LDL-apoB fractional replacement rate, and ASR. In summary, in NASH with cirrhosis, ACCi treatment increases LDL-apoB100 production rate and this effect can be prevented by concurrent fenofibrate therapy.

Abstract An integrated geostatistical methodology for a site-specific reservoir description was used in reservoir simulations to establish additional recovery benefits for gravity drainage infill wells for the Romeo interval for Drill Sites 2 and 5 at Prudhoe Bay. The available geological information varied over multiple scales and included: a detailed chrono-stratigraphic framework relating rocks of similar depositional times, a detailed depositional model with facies associations described at each well from log and core data, and analog outcrop training images obtained using photomosaics. The reservoir description methodology transformed the facies associations at each well into indicator variables and used these variables to analyze vertical and lateral spatial correlation. Conditional truncated gaussian simulation was then used to generate 3D facies association maps within the model area constrained by the chrono-stratigraphic framework. Input from geologists was critical in the evaluation of the geological realism of the computed facies association maps. Porosity and permeability vertical and lateral spatial correlations were then determined for each facies association. Vertical correlation was determined from variogram analysis while lateral correlation was determined from the outcrop training images. Conditional sequential gaussian simulation was then used to distribute 3D porosity and permeability, separately within each facies association, throughout the model area. A pressure solver was used to scale up the 3D fine scale permeability distributions to grid blocks appropriate for direct input into a flow simulation model. The conditional simulation methods allowed the integration of geological information on a number of different scales, thereby capturing the 3D complexity of the Romeo interval. The 3D facies association description generated using this methodology was judged by geologists to depict a very reasonable geological picture of the DS-2,5 Romeo interval. The pressure solver used to scale up the fine scale permeability distributions maintained the major permeability features apparent in the fine scale distribution which were important to reservoir performance.

Corrosion resistance of titanium (Ti) alloys is closely connected with their microstructure which can be adjusted and controlled via different annealing schemes. Herein, we systematically investigate the specific effects of annealing on the corrosion performance of Ti-6Al-3Nb-2Zr-1Mo (Ti80) alloy in 3.5 wt.% NaCl and 5 M HCl solutions, respectively, based on open circuit potential (OCP), potentiodynamic polarization, electrochemical impedance spectroscopy (EIS), static immersion tests and surface analysis. Results indicate that increasing annealing temperature endows Ti80 alloy with a higher volume fraction of β phase and finer α phase, which in turn improves its corrosion resistance. Surface characterization demonstrates that β phase is more resistant to corrosion than α phase owing to a higher content of Nb, Mo, and Zr in the former; additionally, the decreased thickness of α phase alleviates segregation of elements to further restrain the micro-galvanic couple effects between α and β phases. Meanwhile, the influential mechanisms of environmental conditions on corrosion of Ti80 alloy are discussed in detail. As the formation of a highly compact and stable oxide film on surface, annealed Ti80 alloys exhibit a low corrosion current density (10−6 A/cm2) and high polarization impedance (106 Ω⋅ cm2) in 3.5 wt.% NaCl solution. However, they suffer severe corrosion in 5 M HCl solution, resulting from the breakdown of native oxide films (the conversion of TiO2 to aqueous Ti3+), active dissolution of substrate Ti to aqueous Ti3+ and existence of micro-galvanic couple effects. Those findings could provide new insights to designing Ti alloys with high-corrosion resistance through microstructural optimization.