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Investigation of HCAR2 antagonists as a potential strategy to modulate bovine leukocytes

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j.urnal of Animal Science and Biotechnology 2024年第4期15卷 1567-1577页

作者： Laman K.Mamedova Kirby C.Krogstad Paiton O.McDonald Laxman Pokhrel Duy H.Hua evan C.Titgemeyer Barry j.Bradford Department of Animal Science Michigan State UniversityEast LansingMichigan 48824USA Department of Animal Sciences and Industry Kansas State UniversityManhattanKS 66506USA Comparative Medicine and Integrative Biology East LansingMI 48824USA Department of Chemistry Kansas State UniversityManhattanKS 66506USA

Background Dairy cows experiencing ketosis after calving suffer greater disease incidence and are at greater risk of leaving the herd. In vitro administration of beta-hydroxybutyric acid(BHBA;the primary blood ketone) has inhibitory effects on the function of bovine leukocytes. BHBA is a ligand of HCAR2 and the activation of these receptors promotes an anti-inflammatory response which may be related with immunosuppression observed in transition dairy cattle. The obj.ctive of this study was to identify and test antagonists for HCAR2 in bovine immune cells cultured with *** We observed expression of HCAR2 at the protein level within lymphocytes, monocytes, and granulocytes. The proportion of cells expressing HCAR2 tended to be greater in mid-lactation compared to early lactation cows;the increase was a result of increased proportion of T and B cells expressing HCAR2. Stimulation of HCAR2 with niacin or BHBA promoted Ca^(2+) mobilization in neutrophils and mononuclear cells. Mononuclear cells treated with BHBA had diminished intracellular Ca^(2+) responses when HCAR2 was knocked down by si RNA silencing, indicating Ca^(2+) mobilization was mediated by HCAR2 signaling. Two candidate antagonists for HCAR2, synthesized from niacin(NA-1 and NA-5), were tested;monocytes and neutrophils pre-treated with NA-1 and NA-5 had reduced Ca^(2+) mobilization after incubation with BHBA. Furthermore, NA-5 but not NA-1 prevented BHBA-associated reductions in cyclic *** We demonstrated that HCAR2 is present on bovine leukocytes and has greater expression later in lactation. We confirmed that BHBA and niacin derived HCAR2 antagonists alter bovine leukocyte activity. Our results demonstrate that both BHBA and niacin affect bovine leukocyte Ca^(2+) mobilization in a HCAR2-dependent manner.

关键词： Flow cytometry GPR109A HM74A Ketosis

Development of a multivariate empirical model for predicting weak rock mass modulus

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International j.urnal of Mining Science and Technology 2015年第4期25卷 545-552页

作者： Kallu Raj.R. Keffeler evan R. Watters Robert j. Agharazi Alireza Department of Mining Engineering University of Nevada RESPEC Consulting and Services University of Nevada Itasca Houston Inc.

Estimating weak rock mass modulus has historically proven difficult although this mechanical property is an important input to many types of geotechnical analyses. An empirical database of weak rock mass modulus with associated detailed geotechnical parameters was assembled from plate loading tests per- formed at underground mines in Nevada, the Bakhtiary Dam proj.ct, and Portugues Dam proj.ct. The database was used to assess the accuracy of published single-variate models and to develop a multivari- ate model for predicting in-situ weak rock mass modulus when limited geoteehnical data are available. Only two of the published models were adequate for predicting modulus of weak rock masses over lim- ited ranges of alteration intensities, and none of the models provided good estimates of modulus over a range of geotechnical properties. In light of this shortcoming, a multivariate model was developed from the weak rock mass modulus dataset, and the new model is exponential in form and has the following independent variables：（1） average block size or j.int spacing, （2） field estimated rock strength, （3） dis- continuity roughness, and （4） discontinuity infilling hardness. The multivariate model provided better estimates of modulus for both hard-blocky rock masses and intensely-altered rock masses.

关键词： In-situ modulus Weak rock mass Preliminary design Elastic deformation

Predicting the synthesizability of crystalline inorganic materials from the data of known material compositions

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npj.Computational Materials 2023年第1期9卷 733-743页

作者： evan R.Antoniuk Gowoon Cheon George Wang Daniel Bernstein William Cai evan j.Reed Materials Science Division Physical and Life Sciences DirectorateLawrence Livermore National LaboratoryLivermoreCAUSA Department of Chemistry Stanford UniversityStanfordCAUSA Department of Applied Physics Stanford UniversityStanfordCAUSA Google Research Mountain ViewCAUSA Department of Physics Stanford UniversityStanfordCAUSA Department of Mathematics Stanford UniversityStanfordCAUSA Department of Computer Science Stanford UniversityStanfordCAUSA Department of Materials Science and Engineering Stanford UniversityStanfordCAUSA

Reliably identifying synthesizable inorganic crystalline materials is an unsolved challenge required for realizing autonomous materials *** this work,we develop a deep learning synthesizability model(SynthNN)that leverages the entire space of synthesized inorganic chemical *** reformulating material discovery as a synthesizability classification task,SynthNN identifies synthesizable materials with 7×higher precision than with DFT-calculated formation *** a head-to-head material discovery comparison against 20 expert material scientists,SynthNN outperforms all experts,achieves 1.5×higher precision and completes the task five orders of magnitude faster than the best human ***,without any prior chemical knowledge,our experiments indicate that SynthNN learns the chemical principles of charge-balancing,chemical family relationships and ionicity,and utilizes these principles to generate synthesizability *** development of SynthNN will allow for synthesizability constraints to be seamlessly integrated into computational material screening workflows to increase their reliability for identifying synthetically accessible materials.

关键词： inorganic crystalline utilize

Beyond first-line chemotherapy for advanced pancreatic cancer:An expanding array of therapeutic options?

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World j.urnal of Gastroenterology 2014年第9期20卷 2224-2236页

作者： evan j.Walker Andrew H Ko University of California Helen Diller Family Comprehensive Cancer Center San Francisco CA 94115 United States

While an increasing number of therapeutic options are now available for the first-line treatment of locally advanced or metastatic pancreatic cancer,the optimal choice for treatment in the second-line setting and beyond is less well defined.A variety of cytotoxic agents,either alone or in combination,have been evaluated,although primarily in the context of small single-arm or retrospective *** regimens have been associated with median progression-free survival rates in the range of 2-4 mo and overall survival rates between 4-8mo,highlighting the very poor prognosis of patients who are candidates for such *** therapies studied in this chemotherapy-refractory setting,meanwhile,have produced even worse efficacy *** the current article,we review the clinical evidence for treatment of refractory disease,primarily in patients who have progressed on front-line gemcitabine-based *** the process,we highlight the limitations of the available data to date as well as some of the challenges in designing appropriate clinical trials in this salvage setting,including how to select an appropriate control arm given the absence of a wellestablished reference standard,and the importance of incorporating predictive biomarkers and quality of life measures whenever possible into study design.

关键词： Pancreatic cancer Refractory Second-line chemotherapy Gemcitabine

Method of cells-based multiscale modeling of elastic properties of filament wound C/C-SiC including free Si and matrix porosity

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j.urnal of Materials Science & Technology 2019年第12期35卷 2906-2918页

作者： evan j.Pineda Marek Fassin Stefanie Reese j.an-Willem Simon NASA Glenn Research Center 21000 Brookpark RoadMS 49/7ClevelandOH 44135United States Institute for Applied Mechanics RWTH Aachen UniversityMies-van-der-Rohe-Str.152074 AachenGermany

Three different multiscale models, based on the method of cells(generalized and high fidelity) micromechanics models were developed and used to predict the elastic properties of C/C-SiC composites. In particular, the following multiscale modeling strategies were employed: Concurrent modeling of all phases using the generalized method of cells, synergistic(two-way coupling in space) multiscale modeling with the generalized method of cells, and hierarchical(one-way coupling in space) multiscale modeling with the high fidelity generalized method of cells. The three models are validated against data from a hierarchical multiscale finite element model in the literature for a repeating unit cell of C/***, the multiscale models are used in conj.nction with classical lamination theory to predict the stiffness of C/C-SiC plates manufactured via a wet filament winding and liquid silicon infiltration process recently developed by the German Aerospace Institute. Finally, un-reacted Si(or free Si) and porosity in the C matrix are included in the multiscale model, and the effect of these new phases on the stiffness and local stresses are considered.

关键词： Multiscale modeling C/C-SiC Ceramic matrix composites

Theoretical potential for low energy consumption phase change memory utilizing electrostatically-induced structural phase transitions in 2D materials

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npj.Computational Materials 2018年第1期4卷 653-661页

作者： Daniel A.Rehn Yao Li Eric Pop evan j.Reed Department of Mechanical Engineering Stanford UniversityStanfordCA 94305USA Department of Applied Physics Stanford UniversityStanfordCA 94305USA Department of Electrical Engineering Stanford UniversityStanfordCA 94305USA Department of Materials Science and Engineering Stanford UniversityStanfordCA 94305USA

Structural phase-change materials are of great importance for applications in information storage *** driven structural phase transitions are employed in phase-change memory to achieve lower programming voltages and potentially lower energy consumption than mainstream nonvolatile memory ***,the waste heat generated by such thermal mechanisms is often not optimized,and could present a limiting factor to widespread *** potential for electrostatically driven structural phase transitions has recently been predicted and subsequently reported in some two-dimensional materials,providing an athermal mechanism to dynamically control properties of these materials in a nonvolatile fashion while achieving potentially lower energy *** this work,we employ DFT-based calculations to make theoretical comparisons of the energy required to drive electrostatically-induced and thermally-induced phase *** theoretical limits in monolayer MoTe2 and thin films of Ge_(2)Sb_(2)Te_(5),we find that the energy consumption per unit volume of the electrostatically driven phase transition in monolayer MoTe2 at room temperature is 9% of the adiabatic lower limit of the thermally driven phase transition in Ge_(2)Sb_(2)Te_(5).Furthermore,experimentally reported phase change energy consumption of Ge_(2)Sb_(2)Te_(5) is 100–10,000 times larger than the adiabatic lower limit due to waste heat flow out of the material,leaving the possibility for energy consumption in monolayer MoTe2-based devices to be orders of magnitude smaller than Ge_(2)Sb_(2)Te_(5)-based devices.

关键词： transitions phase structural

Uniformly dispersed FeOx atomic clusters by pulsed arc plasma deposition： An efficient electrocatalyst for improving the performance of Li-O2 battery

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Nano Research 2016年第7期9卷 1913-1920页

作者： Xiangyi Luo j.n Lu evan Sohm Lu Ma Tianpin Wu j.anguo Wen Dantong Qiu YunKai Xu Yang Ren Dean j. Miller Khalil Amine Material Sciences Division Argonne National Laboratory Argonne IL 60439 USA Chemical Sciences and Engineering Division Argonne National Laboratory Argonne IL 60439 USA ULVAC Technologies Inc. Methuen MA 01844 USA Center for N anoscale Materials Nanoscience and Technology Argonne National Laboratory Argonne IL 60439 USA Advanced Photon Source Argonne National Laboratory Argonne IL 60439 USA Center for Nanoscale Materials Nanoscience and Technology Argonne Notional Laboratory Argonne IL 60439 USA

The present study explored a new method to improve the catalytic activity of non-precious metals, especially in electrochemical reactions. Highly ionized Fe plasma produced by arc discharge was uniformly deposited on a porous carbon substrate and formed atomic clusters on the carbon surface. The as-prepared FeO~/C material was tested as a cathode material in a rechargeable Li-02 battery under different current rates. The results showed significant improvement in battery performance in terms of both cycle life and reaction rate. Furthermore, X-ray diffraction （XRD） and scanning electron microscopy （SEM） results showed that the as-prepared cathode material stabilized the cathode and reduced side reactions and that the current rate was a critical factor in the nucleation of the discharge products.

关键词： Li-O2 battery FeOx atomic cluster electrocatalyst pulsed arc plasmadeposition (APD)

From Slater to Mott physics by epitaxially engineering electronic correlations in oxide interfaces

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npj.Computational Materials 2021年第1期7卷 846-851页

作者： Carla Lupo evan Sheridan Edoardo Fertitta David Dubbink Chris j.Pickard Cedric Weber Theory and Simulation of Condensed Matter King’s College LondonLondonUK Happy Electron Ltd LondonUK Department of Materials Science and Metallurgy University of CambridgeCambridgeUK Advanced Institute for Materials Research Tohoku UniversitySendaiJapan

Using spin-assisted ab initio random structure searches,we explore an exhaustive quantum phase diagram of archetypal interfaced Mott insulators,***-iron and lanthanum-titanium *** particular,we report that the charge transfer induced by the interfacial electronic reconstruction stabilises a high-spin ferrous Fe2+*** provide a pathway to control the strength of correlation in this electronic state by tuning the epitaxial strain,yielding a manifold of quantum electronic phases,***-Hubbard,charge transfer and Slater insulating ***,we report that the electronic correlations are closely related to the structural oxygen octahedral rotations,whose control is able to stabilise the low-spin state of Fe2+at low pressure previously observed only under the extreme high pressure conditions in the Earth’s lower ***,we provide avenues for magnetic switching via THz radiations which have crucial implications for next generation of spintronics technologies.

关键词： Slater lanthanum quantum

Leaching of lanthanide and yttrium from a Central Appalachian coal and the ashes obtained at 550-950℃

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j.urnal of Rare Earths 2022年第5期40卷 807-814,I0005页

作者： Ronghong Lin Yee Soong Bret H.Howard Murphy j.Keller Elliot A.Roth Ping Wang evan j.Granite U.S.Department of Energy National Energy Technology Laboratory626 Cochrans Mill RoadP.O.Box 10940PittsburghPA15236United States Keylogic Systems.Pittsburgh PA15236United States

In this work,we investigated leaching of lanthanide and yttrium(REY) from a Central Appalachian coal and its ashes obtained at 550-950℃ with the main purpose of understanding the impact of ashing temperature on REY leachability in water,ammonium sulfate,and hydrochloric *** is found that the coal contains a negligible amount of water-soluble REY,less than 1% ion-exchangeable REY,and about 28% of HCl-soluble *** leads to dramatic changes in REY leachability in both ammonium sulfate and hydrochloric acid solutions,which is believed to be related to transformation and redistribution of organically-associated REY in coal during the ashing *** temperature significantly affects REY leaching from coal ashes;higher ashing temperature results in lower REY leachability in both *** minerals may play a significant role in changing the leachability of REY after *** addition,the results also suggest that the organic matter in the coal is relatively enriched in heavy REY.

关键词： Acid leaching Cation exchange Coal Coal ash Rare earth elements Yttrium