Pyrazole-Based Lactate Dehydrogenase Inhibitors with Optimized Cell Activity and Pharmacokinetic Pro
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Mechanical force applied to bone produces two localized mechanical signals on the cell: deformation of the extracellular matrix (substrate strain) and extracellular fluid flow. To study the effects of these stimuli on osteoblasts, MC3T3-E1 cells were grown on type I collagen-coated plastic plates and subjected to four-point bending. This technique produces uniform levels of physiological strain and fluid forces on the cells. Each of these parameters can be varied independently. Osteopontin (OPN) mRNA expression was used to assess the anabolic response of MC3T3-E1 cells. When fluid forces were low, neither strain magnitude nor strain rate was correlated with OPN expression. However, higher-magnitude fluid forces significantly increased OPN message levels independently of the strain magnitude or rate. These data indicate that fluid forces, and not mechanical stretch, influence OPN expression in osteoblasts and suggest that fluid forces induced by extracellular fluid flow within the bone matrix may play an important role in bone formation in response to mechanical loading.
The Moment Preserving Constrained Resampling (MPCR) algorithm for particle resampling is introduced and applied to particle-in-cell (PIC) methods to increase simulation accuracy, reduce compute cost, and/or avoid numerical instabilities. The general algorithm partitions the system space into smaller subsets and resamples the distribution within each subset. Further, the algorithm is designed to conserve any number of particle and grid moments with a high degree of accuracy (i.e. machine accuracy). The effectiveness of MPCR is demonstrated with several numerical tests, including a use-case study in gyrokinetic fusion plasma simulations. Finally, the computational cost of MPCR is negligible compared to the cost of particle evolution in PIC methods, and the tests demonstrate that periodic particle resampling yields a significant improvement in the accuracy and stability of the results.
We use the global gyrokinetic stellarator code XGC-S to look at turbulence physics in geometry of the proposed quasi-axisymmetric stellarator, QUASAR. In this article, the XGC-S code is first verified for nonlinear simulations of ion temperature gradient-driven turbulence by a successful benchmark with the established nonlinear tokamak code XGC1 in a CYCLONE-like tokamak case. We then apply the XGC-S code to QUASAR for nonlinear turbulence physics. We find that the highly poloidally localized linear mode gives way to a more evenly distributed nonlinear turbulent structure. Furthermore, the radial extent of the mode increases and occupies a large fraction of the volume, despite the initially localized temperature profile, as the profiles relax.
Transition metal (TM) ions, commonly Ni and Mn, play a crucial role in Li-ion battery cathodes as the reaction centers for rapid redox reactions. A major challenge with TM-based cathodes is capacity degradation, particularly at higher operating voltages. This degradation is closely linked to the dissolution of TMs from the cathode materials and their subsequent deposition on the anode. This process not only modifies the surface structure of the cathode but, more significantly, alters the SEI composition on the anode [1-2]. The dissolution of TMs cations into a liquid electrolyte from cathode materials, such as Mn-ion dissolution from Mn-rich cathode (LMR), is detrimental to the cycling performance of Li-ion batteries [3-4]. Much attention has been paid to this issue but there remains a lack of characterization techniques which can detect the TM-ion dissolution from the cathode during electrochemical measurements. In our study, we use in-situ ATR-FTIR as an effective technique to probe the TM-ion dissolution from the cathode. We have first demonstrated the detrimental effects of TM ions on the electrochemical performance of Li-ion batteries by adding a small amount of TM salt (50 mM Mn(PF6)) to the electrolyte of a Li-ion coin cell with LFP and graphite electrode. We observed a rapid capacity fade after the first delithiation cycle. To investigate TM ion dissolution, we established a baseline IR spectrum for various TM solvation states (such as Mn and Ni) by measuring concentration-dependent IR spectra. This baseline spectrum helps us detect TM ion dissolution during battery cycling. In this work, we discuss in detail the effect of TM ions on the electrochemical performance of Li-ion batteries and the detection of TM ions during battery cycling using in-situ FTIR spectroscopy. We will compare TM dissolution between coated and uncoated cathodes to examine the effect of cathode coatings to mitigate degradation due to TM dissolution and cross-over from cathode to anode. References: (1) Zhan, C.; Wu, T.; Lu, J.; Amine, K. Dissolution, migration, anddeposition of transition metal ions in Li-ion batteries exemplified byMn-based cathodes - a critical review. Energy Environ. Sci. 2018, 11,243-257. (2) Jung, R.; Linsenmann, F.; Thomas, R.; Wandt, J.; Solchenbach,S.; Maglia, F.; Stinner, C.; Tromp, M.; Gasteiger, H. A. Nickel,Manganese, and Cobalt Dissolution from Ni-Rich NMC and TheirEffects on NMC622-Graphite Cells. J. Electrochem. Soc. 2019, 166,A378-A389. (3) Zhao, L.; Chenard, E.; Capraz, O. O.; Sottos, N. R.; White, S.R. Direct Detection of Manganese Ions in Organic Electrolyte by UV-Vis Spectroscopy. J. Electrochem. Soc. 2018, 165, A345-A348 (4) Zhang, Y.; Hu, A.; Xia, D.; Hwang, S.; Sainio, S.; Nordlund, D.;Michel, F. M.; Moore, R. B.; Li, L.; Lin, F. Operando characterization and regulation of metal dissolution and redeposition dynamics nearbattery electrode surface. Nat. Nanotechnol. 2023, 18, 790.
H2@Scale is one of EERE's flagship initiatives to enable clean and affordable hydrogen production, storage, distribution, and utilization across multiple sectors in the economy. The January H2IQ hour will discuss results from a recent multi-laboratory analysis report quantifying the technical and economic potential of H2@Scale, given the use of hydrogen as an energy intermediate to integrate sectors in the U.S. energy system. Mark Ruth of the National Renewable Energy Laboratory, the lead author of the report, will discuss specific examples of the role hydrogen can play in industry and transportation sectors, such as steelmaking, synthetic fuels, and blending into natural gas pipelines. He will also explain how hydrogen production can be integrated with the electric grid to monetize low-cost energy and incentivize growth in renewable energy supply. The H2IQ Hour will dive into estimates for future hydrogen consumption in current and emerging sectors, given R&D advances and varying prices of natural gas and electricity.
Mechanical loading stimulates many responses in bone and osteoblasts associated with osteogenesis. Since loading and parathyroid hormone (PTH) activate similar signaling pathways in osteoblasts, we postulate that PTH can potentiate the effects of mechanical stimulation. Using an in vitro four-point bending device, we found that expression of COX-2, the inducible isoform of cyclooxygenase, was dependent on fluid forces generated across the culture plate, but not physiologic levels of strain in MC3T3-E1 osteoblast-like cells. Addition of 50 nM PTH during loading increased COX-2 expression at both subthreshold and threshold levels of fluid forces compared with either stimuli alone. We also demonstrated that application of fluid shear to MC3T3-E1 cells induced a rapid increase in [Ca(2+)](i). Although PTH did not significantly change [Ca(2+)](i) levels, flow and PTH did produce a significantly greater [Ca(2+)](i) response and increased the number of responding cells than is found in fluid shear alone. The [Ca(2+)](i) response to these stimuli was significantly decreased when the mechanosensitive channel inhibitor, gadolinium, was present. These studies indicate that PTH increases the cellular responses of osteoblasts to mechanical loading. Furthermore, this response may be mediated by alterations in [Ca(2+)](i) by modulating the mechanosensitive channel.
Phonon-derived behaviors are important indicators of novel phenomena in transition metal trihalides, including spin liquid behavior, two-dimensional magnetism, and spin-lattice coupling. However, phonons and their dependence on spin structure and excitations have not been adequately explored. In this work, we probe and critically examine the vibrational properties of the prototype ferromagnetic honeycomb lattice material CrCl 3 using inelastic neutron scattering and density functional theory. We demonstrate that magnetic and van der Waals interactions are essential to describing the structure and phonons in CrCl 3 ; however, the specific spin configuration is unimportant. Further, this provides context for understanding thermal transport measurements as governed by dynamical spin-lattice couplings. More importantly, we introduce an efficient dynamic method that exploits translational symmetries in large conventional unit cells that generates insights into phonon dispersions, interactions, and measured spectra in terms of quantum phase interference conditions. This work opens new avenues for understanding phonons in layered magnets and more generally in conventional cell geometries of a variety of materials.
Cost-effective production of the highly effective anti-cancer drug, paclitaxel (Taxol ® ), remains limited despite growing global demands. Low yields of the critical taxadiene precursor remains a key bottleneck in microbial production. In this study, the key challenge of poor taxadiene synthase (TASY) solubility in S. cerevisiae was revealed, and the strains were strategically engineered to relieve this bottleneck. Multi-copy chromosomal integration of TASY harbouring a selection of fusion solubility tags improved taxadiene titres 22-fold, up to 57 ± 3 mg/L at 30 °C at microscale, compared to expressing a single episomal copy of TASY. The scalability of the process was highlighted through achieving similar titres during scale up to 25 mL and 250 mL in shake flask and bioreactor cultivations, respectively at 20 and 30 °C. Maximum taxadiene titres of 129 ± 15 mg/L and 127 mg/L were achieved through shake flask and bioreactor cultivations, respectively, of the optimal strain at a reduced temperature of 20 °C. The results of this study highlight the benefit of employing a combination of molecular biology and bioprocess tools during synthetic pathway development, with which TASY activity was successfully improved by 6.5-fold compared to the highest literature titre in S. cerevisiae cell factories.
Superconducting radio frequency (SRF) cavities are fundamental building blocks of modern particle accelerators. A surface resistance in the tens of nanoOhm range is achieved when cooling these cavities to liquid helium temperature, ~2 - 4 K. One of the leading sources of residual losses in SRF cavities is trapped magnetic flux. Flux trapping mechanism depends on different surface preparations and cool-down conditions. We have designed, developed and commissioned a combined magnetic and temperature mapping system using anisotropic magneto-resistance sensors and carbon resistors, respectively, to study the flux trap mechanism in 3 GHz single-cell niobium cavities. In this contribution, we will describe the experimental apparatus and present preliminary test results.
Fuel cell electrolyte properties - solubility of hydrogen and oxygen in KOH and LiOH, diffusivity of oxygen and hydrogen in KOH, and density and vapor pressure of KOH and LiOH
Space program scenarios for production of large space structures from lunar materials are defined. The concept of the space manufacturing facility (SMF) is presented. The manufacturing processes and equipment for the SMF are defined and the conceptual layouts are described for the production of solar cells and arrays, structures and joints, conduits, waveguides, RF equipment radiators, wire cables, and converters. A 'reference' SMF was designed and its operation requirements are described.
A 3.5 in. diameter, nominal 15A h cell went into advanced development in 1976 and is still in advanced development. The development of common pressure vessel nickel hydrogen modules is explored. The concept is to put a number of nickel hydrogen cells into one pressure vessel. There is a very modest advantage in terms of weight energy density, but a substantial advantage in both volume energy density and cost.
Design parameters for two large area, low cost solar cells are presented, and electron irradiation testing, thermal alpha testing, and cell processing are discussed. The devices are a 2 ohm-cm base resistivity silicon cell with an evaporated aluminum reflector produced in a dielectric wraparound cell, and a 10 ohm-cm silicon cell with the BSF/BSR combination and a conventional contact system. Both cells are 5.9 x 5.9 cm and require 200 micron thick silicon material due to mission weight constraints. Normalized values for open circuit voltage, short circuit current, and maximum power calculations derived from electron radiation testing are given. In addition, thermal alpha testing values of absorptivity and emittance are included. A pilot cell processing run produced cells averaging 14.4% efficiencies at AMO 28 C. Manufacturing for such cells will be on a mechanized process line, and the area of coverslide application technology must be considered in order to achieve cost effective production.
The effects of exposing 23 specimens of optical and thermal control materials to space at 120 km altitude for over 40 hrs during the STS-8 mission are discussed. Ten samples of paint targeted for the Space Telescope (ST) and the Tethered Satellite were exposed, and included polyurethane, oxide, silicone, and glossy black and white samples which were scanned for alterations in the optical properties after being retrieved. Nine mirror-type materials were also investigated, along with silver specimens typical of solar cell interconnects. The oxygen flow at the orbital altitude was 3.5 x 10 to the 20th atoms/cu cm. The exposures caused no degradation of the magnesium fluoride mirror coatings, while the Kapton coating for the ST solar cell panels showed evidence of losing thickness. The Ag solar cell contacts will require coatings to extend their lifetimes. Overcoatings were also proven necessary for inhibiting degradation of painted surfaces.
The 8-cm x 8-cm gridded back cell being developed for the space station photovoltaic array is described. Modeling studies show that the beginning of life power output of 1.039 W per cell may be met by several different configurations, the most promising being either a fielded or nonfielded 2 ohm-cm planar 8-mil cell. Experimental data are presented which show that a thermal alpha of 0.63 is achievable on a planar cell but at the expense of some Isc. Planar cells are found to possess short-circuit currents which are 9 percent lower than on textured cells due to the loss of near-IR radiation by transmission through the cell. Preliminary modeling shows that the efficiency of the textured cell exceeds the planar cell by approximately 9 percent at 25 C but the situation is reversed in orbit due to the high thermal alpha of textured cells (0.82). Experimental data show that the IR absorption in textured cells can be reduced by about 3 alpha points without loss of efficiency by controlling the doping concentration in the diffused layers, thus increasing the efficiency in orbit.
A growing number of species require conservation or management efforts. Success of these activities requires knowledge of the species' occurrence pattern. Species-habitat models developed from GIS data sources are commonly used to predict species occurrence but commonly used data sources are often developed for purposes other than predicting species occurrence and are of inappropriate scale and the techniques used to extract predictor variables are often time consuming and cannot be repeated easily and thus cannot efficiently reflect changing conditions. We used digital orthophotographs and a grid cell classification scheme to develop an efficient technique to extract predictor variables. We combined our classification scheme with a priori hypothesis development using expert knowledge and a previously published habitat suitability index and used an objective model selection procedure to choose candidate models. We were able to classify a large area (57,000 ha) in a fraction of the time that would be required to map vegetation and were able to test models at varying scales using a windowing process. Interpretation of the selected models confirmed existing knowledge of factors important to Florida scrub-jay habitat occupancy. The potential uses and advantages of using a grid cell classification scheme in conjunction with expert knowledge or an habitat suitability index (HSI) and an objective model selection procedure are discussed.