gebhart/patrepeval huggingface dataset:
Structural specificity in the suppression of HMG-CoA reductase in human fibroblasts by intermediates in bile acid biosynthesis. (1995)

The effect of bile acid precursors on the activity of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase was investigated. Cholesterol and 34 of its derivatives, including 23 potential intermediates in bile acid biosynthesis, were incubated with cultures of human fibroblasts for 24 h in the absence or presence of lipoproteins, and the activity of HMG-CoA reductase was then determined. In the absence of lipoproteins, many of the bile acid intermediates were inhibitory at a high concentration (2.5 microM), while only three, 27-hydroxycholesterol, 7 alpha, 27-dihydroxy-4-cholesten-3-one, and 7 alpha, 12 alpha, 27-trihydroxy-4-cholesten-3-one, caused a significant suppression at lower concentrations (often > 80% suppression at 0.25 microM). Even at 0.06 microM these sterols caused > 50% suppression of the enzyme activity. In addition, 27-hydroxy-4-cholesten-3-one, not usually considered to be an intermediate in bile acid biosynthesis, was a very potent inhibitor. Comparative studies showed that the effect of the three bile acid precursors was similar to that of 25-hydroxy-, 24-hydroxy-, and 7-oxo-cholesterol and 3 beta-hydroxy-5 alpha-cholest-8(14)-en-15-one. The presence of lipoproteins decreased or eliminated the inhibitory effect of most intermediates. Studies of the metabolism of the three most potent inhibitors in the fibroblasts indicated that the suppression was due to the compounds per se and not to products of their metabolism. The results show that a few specific intermediates in the formation of bile acids are potent suppressors of HMG-CoA reductase.(ABSTRACT TRUNCATED AT 250 WORDS)
Old Drugs for a New Virus: Repurposed Approaches for Combating COVID-19 (2020)

There is a large global unmet need for effective countermeasures to combat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19). The development of novel antiviral drugs is expensive and too slow to meet the immediate need. The repurposing of drugs that are approved or are under advanced clinical investigation provides a cost- and time-effective therapeutic solution. This review summarizes the major repurposed approaches that have been proposed or are already being studied in clinical trials for COVID-19. Among these approaches are drugs that aim to reduce SARS-CoV-2 replication by targeting either viral enzymatic functions or cellular factors required for the viral life cycle. Drugs that modulate the host immune response to SARS-CoV-2 infection by boosting it to enhance viral clearance or by suppressing it to prevent excessive inflammation and tissue injury represent another category. Lastly, we discuss means to discover repurposed drugs and the ongoing challenges associated with the off-label use of existing drugs in the context of the COVID-19 outbreak.
Glucosylceramide synthase inhibitors D-PDMP and D-EtDO-P4 decrease the GM3 ganglioside level, differ in their effects on insulin receptor autophosphorylation but increase Akt1 kinase phosphorylation in human hepatoma HepG2 cells. (2016)

Gangliosides function as modulators of several cell growth related receptors. It was shown for caveolin-rich adipocytes, that GM3 ganglioside binds to insulin receptor (IR), dissociates its complex with caveolin, and thus lowers IR autophosphorylation following insulin treatment. We extended those studies into human hepatocyte-derived HepG2 cells, characterized by a high level of IR but low of caveolin. To lower the glycosphingolipid content, estimated by GM3 concentration, two glucosylceramide synthase inhibitors d-threo-1-pheny-2-decanoylamino-3-morpholino-1-propanol (d-PDMP) and d-threo-1-(3,4,-ethylenedioxy)phenyl-2-palmitoylamino-3-pyrrolidino-1-propanol (d-EtDO-P4) were used. d-PDMP at 40 µM or d-EtDO-P4 at 1 µM concentrations in culture medium decreased the GM3 content to 22.3% (17.8-26.1%) and 18.1% (13.7-24.4%), respectively, of the control value. The reduction of GM3 obtained with d-PDMP was accompanied by a 185.1% (153.5-423.8%) significant increase in the level of IR autophosphorylation following cell stimulation with 100 nM insulin. The effect of d-EtDO-P4 on IR autophosphorylation was smaller amounting to an increase by 134.8% (111.3-167.8%) of the control level and statistically non-significant. The effects of d-PDMP and d-EtDO-P4 could also be detected at the level of Akt1 kinase. In cells grown in the presence of d-PDMP the level of phosphorylated Akt1 was 286.0% (151.4%-621.1%) of that in the control. In this case the effect of d-EtDO-P4 was similar: 223.0% (181.4-315.4%) significant increase in phosphorylated Akt1. We assume that glycosphingolipid depletion in HepG2 cells may affect not only IR autophosphorylation but also, independently, the phosphorylation of Akt1, by modifying the membrane microenvironment of this kinase.
Accurate thermal analysis considering nonlinear thermal conductivity (2006)

The increase in packing density has led to a higher power density in the chip which in turn has led to an increase in temperature on the chip. Temperature affects reliability, performance and power directly, motivating the need to accurately simulate the thermal profile of a chip. In literature, thermal conductivity is assumed to be a constant in order to obtain a linear system of equations which can be solved efficiently. But thermal conductivity is a nonlinear function of temperature and for silicon it varies by 22% over the range 27-80deg C (McConnell et al., 2001). If the nonlinearity of the thermal conductivity is ignored the thermal profile might be off by 10deg C. Thus to get an accurate thermal profile it is important to consider the nonlinear dependence of the thermal conductivity on temperature. In this work the nonlinear system arising out of considering the nonlinear thermal conductivity is solved efficiently using a variant of Newton-Raphson. We also study the abstraction levels under which the approximation of a periodic source by a DC source is valid
Synthesis, structure and luminescence of 1,8-diaurionaphthalenes (2010)

Reaction of 1,8-dilithionaphthalene with [AuCl(Et3P)] or [Au2Cl2(μ-dppm)] (dppm = bis(diphenylphosphinomethane)) in Et2O/THF leads to formation of bis(triethylphosphine)-1,8-diaurionaphthalene (1) and dppm-1,8-diaurionaphthalene (2), respectively. The dppm ligand present in complex 2 bridges the two gold centers leading to formation of short intramolecular Au–Au distances of av. 2.85 Å. Complex 2 reacts with AgPF6 in THF/CH2Cl2 to afford a dicationic Au4Ag2 complex which has been isolated as the bis(hexafluorophosphate) salt (3). In this cluster, two molecules of 2 sandwich two Ag cations resulting in the formation of a Au2AgAu2Ag six-membered ring in which the metal centers are connected by Au–Au (av. 2.84 Å) and Au–Ag (av. 2.75 Å) metallophilic interactions. This cluster is further stabilized by short Ag–C interactions involving some of the naphthalene carbon atoms. The luminescence spectra of 2 and 3 have been recorded. Both complexes display relatively broad emission bands centered at 540 nm which result, at least in part, from the heavy atom induced phosphorescence of the naphthalene chromophore.
ChemInform Abstract: Use of Acyclic Glycosyl Donors for Furanoside Synthesis. (1997)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Phase Behavior of an Extended Surfactant in Water and a Detailed Characterization of the Dilute and Semidilute Phases (2009)

The formation of microemulsions with triglycerides under ambient conditions has been a challenge for scientists for many decades. For this reason, so-called extended surfactants were developed that contained hydrophilic/lipophilic linkers to stretch further into the oil and water phase, and enhance the solubility of triglycerides in water. Currently, only limited information about the properties of these surfactants and its behavior in water is available. Therefore, in this work, mixtures of a chosen extended surfactant (C(12-14)-PO(16)-EO(2)-SO(4)Na, X-AES) with H(2)O/D(2)O over the whole concentration range were studied by optical microscopy. A schematic phase diagram has been obtained, which shows two isotropic liquid phases at the lowest and highest surfactant concentrations. Furthermore, between the isotropic solutions, four liquid-crystalline phases occur: a hexagonal phase (H(1)), a lamellar phase (L(alpha)) with a change in birefringence, a bicontinuous cubic phase (V(2)), and a reverse hexagonal phase (H(2)). The structure of the micellar solution (L(1)) was determined by cryo-TEM, dynamic light scattering, and (1)H NMR, which gave information about the size, the aggregation number, and the area per molecule of the micelles. Liquid-crystal formation occurs from the micellar solution in two different ways. The first route appeared by increasing the temperature, going from an L(1) to an L(alpha) phase. By increasing the surfactant concentration (at low temperatures), a second route showed a transition from L(1) to H(1). In addition, the effect of sodium chloride on the cloud point of the extended surfactant was examined, indicating that small amounts of NaCl have no influence on the phase behavior. The monolayer behavior of the extended surfactant at the air-water interface was also determined. Despite its water solubility, an isotherm on the water subphase was found, showing slow kinetics of the molecules to go into the bulk. Thus, the determination of the cmc of the extended surfactant using conventional methods was found to be impossible.
Active Diffusion of Nanoparticles of Maternal Origin Within the Embryonic Brain (2016)

PSi NPs penetrate deep in the brain tissues of embryos after intraventricular injection and after iv. injection to the mother.
Laser Engineered Net Shaping (LENS(TM)): A Tool for Direct Fabrication of Metal Parts (1998)

For many years, Sandia National Laboratories has been involved in the development and application of rapid prototyping and dmect fabrication technologies to build prototype parts and patterns for investment casting. Sandia is currently developing a process called Laser Engineered Net Shaping (LENS~) to fabricate filly dense metal parts dwectly from computer-aided design (CAD) solid models. The process is similar to traditional laser-initiated rapid prototyping technologies such as stereolithography and selective laser sintering in that layer additive techniques are used to fabricate physical parts directly from CAD data. By using the coordinated delivery of metal particles into a focused laser beam apart is generated. The laser beam creates a molten pool of metal on a substrate into which powder is injected. Concurrently, the substrate on which the deposition is occurring is moved under the beam/powder interaction zone to fabricate the desired cross-sectiwal geometry. Consecutive layers are additively deposited, thereby producing a three-dmensional part. This process exhibits enormous potential to revolutionize the way in which metal parts, such as complex prototypes, tooling, and small-lot production parts, are produced. The result is a comple~ filly dense, near-net-shape part. Parts have been fabricated from 316 stainless steel, nickel-based alloys, H13 tool steel, and titanium. This talk will provide a general overview of the LENS~ process, discuss potential applications, and display as-processed examples of parts.
ChemInform Abstract: C‐Glycosylation of Cyclic N‐Acyliminium Ions with Trimethylsilyloxyfuran. (1997)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Spectrally Flattened, Broadband Astronomical Frequency Combs (2015)

We demonstrate the generation of broadband, visible astronomical frequency combs with flattened spectral envelopes. The flat-top region of the spectrum ranges from about 450 to 730 nm, at mode spacings of 18 and 25 GHz.
Hyperbolic functions (2006)

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&lt;title&gt;Detection of cracks under cladding using magneto-optic imaging and rotating in-plane magnetization&lt;/title&gt; (1996)

Conventional nondestructive inspection (NDI) of steel components, using magnetic particle, flux-leakage or near surface ultrasonic methods, is rendered difficult by the presence of protective coatings such as paint or stainless- steel cladding. Thick-section nuclear reactor pressure vessels (RPVs), having as-welded cladding up to 0.25 inches thick are a case in point. Here, magnetic particle techniques do not work and ultrasonic techniques are difficult to apply because of cladding roughens and variable elastic properties in the cladding and the weld interface. An NDI technique that is essentially unaffected by standard thicknesses of protective coatings would be a major advance. Magneto-optic imaging is one such technique. While conventional magneto-optic/eddy current imagers (MOIs) are a proven technology in the NDI of nonferromagnetic conductors, they do not possess a self-contained method for magnetizing steel. The purpose of this work was to develop methods for producing rotating, in-plane magnetization and then combine this technology with magneto-optic imaging to produce a self-contained instrument capable of real-time imaging of cracks in steel through protective coatings. We successfully demonstrated rotating in-plane magnetization using special 'quadrature' magnetic-yokes designed to accommodate both flat and cylindrical steel surfaces. The yokes were attached one at a time, to an MOI of reduced size, and the combined system was placed on a sample of the appropriate curvature containing cracks. A two-channel power amplifier was used to drive the yoke coils in quadrature. The resulting crack images were found to be much less sensitive to liftoff than conventional magnetic particle or flux-leakage NDI. In particular, cracks in steel were successfully imaged through 0.125 inches of stainless-steel cladding, making it likely that images of cracks in steel under even thicker cladding should be possible after further development of the technology. Unlike conventional magnetic particle or flux- leakage NDI, where crack orientation is important, rotating in-plane magnetization renders crack orientation irrelevant. Finally, because of these successes, the new NDI technology for steel should find many important applications.
Synthesis and dopaminergic activity of some halogenated mono- and dihydroxylated 2-aminotetralins (1986)

In a series of 7,8-dihydroxy-1-phenyltetrahydro-3-benzazepine dopamine receptor agonists introduction of a chloro or fluoro substituent into the 6-position increases dopaminergic potency. Also, in this series replacement of the 7-hydroxyl group with a halogen results in inversion of activity from dopamine receptor agonist to antagonist. The present study was aimed at exploring the possibility that the structure-activity observations in the 3-benzazepine series of dopaminergic agents might be extrapolated to another class of dopamine receptor agonists, the 2-aminotetralins. Thus, a series of chloro- and fluoro-substituted mono- and dihydroxylated 2-aminotetralins was prepared and evaluated for dopaminergic properties in D-1 and D-2 receptor-related tests. Introduction of a chloro substituent into the 8-position of the prototype of this series, i.e. 2-amino-6,7-dihydroxytetralin (ADTN), resulted in a compound with a high degree of selectivity for the D-1 subpopulation of dopamine receptors; it was equally or more potent than ADTN in the D-1 receptor-related tests with greatly decreased effectiveness in the tests involving D-2 receptors. A similar effect was observed with 8-fluoro-ADTN; however, the N-(4-hydroxyphenethyl)-N-propyl derivative 4g of the 8-chloro-substituted ADTN showed marked D-2 binding affinity. Conversely, introduction of a chloro substituent into the 5-position of ADTN markedly decreased D-1 receptor affinity and efficacy. This effect was not seen with the related 5-fluoro derivative, suggesting D-1 receptors are more sensitive to bulk in the 5-position of ADTN than are the D-2 receptors. Replacement of either the 6- or 7-hydroxyl groups of ADTN with a chloro or fluoro substituent, in contrast, did not parallel the response seen in the benzazepine series (i.e., the compounds uniformly demonstrated less receptor affinity and did not have dopamine receptor antagonist activity); however, the decrease in agonist potency was less marked in the case of 2-amino-6-fluoro-7-hydroxytetralins than in the chlorinated monohydroxyaminotetralins. Thus, a parallelism in structure-activity relationships in the benzazepine and aminotetralin series of dopamine receptor agonists was not observed. The differences may reflect altered modes of receptor binding in the two series.
Representation of Stimulus Speed and Direction in Vibrissal-Sensitive Regions of the Trigeminal Nuclei: A Comparison of Single Unit and Population Responses (2016)

The rat vibrissal (whisker) system is one of the oldest and most important models for the study of active tactile sensing and sensorimotor integration. It is well established that primary sensory neurons in the trigeminal ganglion respond to deflections of one and only one whisker, and that these neurons are strongly tuned for both the speed and direction of individual whisker deflections. During active whisking behavior, however, multiple whiskers will be deflected simultaneously. Very little is known about how neurons at central levels of the trigeminal pathway integrate direction and speed information across multiple whiskers. In the present work, we investigated speed and direction coding in the trigeminal brainstem nuclei, the first stage of neural processing that exhibits multi-whisker receptive fields. Specifically, we recorded both single-unit spikes and local field potentials from fifteen sites in spinal trigeminal nucleus interpolaris and oralis while systematically varying the speed and direction of coherent whisker deflections delivered across the whisker array. For 12/15 neurons, spike rate was higher when the whisker array was stimulated from caudal to rostral rather than rostral to caudal. In addition, 10/15 neurons exhibited higher firing rates for slower stimulus speeds. Interestingly, using a simple decoding strategy for the local field potentials and spike trains, classification of speed and direction was higher for field potentials than for single unit spike trains, suggesting that the field potential is a robust reflection of population activity. Taken together, these results point to the idea that population responses in these brainstem regions in the awake animal will be strongest during behaviors that stimulate a population of whiskers with a directionally coherent motion.
Separation and Purification of 2,5-Dimethylfuran: Process Design and Comparative Technoeconomic and Sustainability Evaluation of Simulated Moving Bed Adsorption and Conventional Distillation (2020)

The furanic chemical 2,5-dimethylfuran (DMF) is an attractive biobased fuel and feedstock. High-yield biphasic processes for DMF synthesis from sugars employ higher alcohols such as n-butanol (BuOH) as solvents. This leads to a product containing <8 wt % DMF and byproducts in the BuOH solvent along with water. DMF process economics are dominated by separation costs for DMF purification and recycle of BuOH and water. We previously demonstrated efficient adsorptive separation of DMF with a stable ZIF-8 metal–organic framework adsorbent. Here, we present a detailed, comparative technoeconomic analysis and sustainability indicators of adsorptive versus conventional distillation separation processes to produce 98 wt % pure DMF at 100 metric tons/day. The novel adsorptive process integrates a simulated moving bed (SMB) unit with water removal and desorbent recovery systems, whereas the distillation process relies on multiple columns operating at different pressures to handle the strongly nonideal multicomponent thermodynamics. Rigorous process modeling is conducted by a combination of the Aspen Plus flowsheet simulation package and our in-house SMB modeling and optimization package, with realistic multicomponent adsorption and vapor–liquid equilibrium models parametrized by experimental data. This is followed by detailed calculations and sensitivity analysis of bare-module, utility, and material costs. The net present values (NPVs) of the process alternatives show a clear long-term economic advantage of the adsorptive process, mainly due to large reduction in utility costs. For a 100 MTD DMF plant, the ΔNPV for adsorptive separation is strongly positive (>$6M at a 10% discount rate and 15-year operation) and remains competitive over a large range of sensitivity factors. When translated to a large potential DMF biofuel market size similar to that of bioethanol, the SMB-based adsorptive process would save >$8B/yr. globally in separation costs. Furthermore, the novel adsorptive process has much better sustainability indicators, including 41% lower process energy intensity and 37% lower process CO2 emissions, as well as a number of qualitatively determined environmental and safety advantages.
Compact, low-cost, and broadband terahertz time-domain spectrometer (2023)

Terahertz time-domain spectroscopy (THz-TDS) is a powerful technique that enables the characterization of a large range of bulk materials, devices, and products. Although this technique has been increasingly used in research and industry, the standard THz-TDS configuration relying on the use of a near-infrared (NIR) laser source remains experimentally complex and relatively costly, impeding its availability to those without the expertise to build a high-performance setup based on nonlinear optics or without the financial means to acquire a commercial unit. Broadband THz-TDS systems require an even larger financial investment, primarily because the generation and detection of spectral components exceeding 3 THz typically need an ultrafast NIR source delivering sub-100-fs pulses. Such an ultrafast source can be bulky and cost upwards of <i>$</i>100,000. Here, we present a broadband, compact, and portable THz-TDS system comprising three modules that allow for the implementation of a single low-cost ultrafast laser, hence significantly decreasing the overall cost of the system. In the first module, the output laser pulses are spectrally broadened through nonlinear propagation in a polarization-maintaining optical fiber and then temporally compressed to achieve a higher peak power. The other two modules utilize thick nonlinear crystals with periodically patterned surfaces that diffract NIR pulses and optimize the efficiency of THz generation and detection processes by enabling a noncollinear beam geometry. Phase-matching conditions in the nonlinear crystals are controlled by the period of the gratings to gain access to a large spectral THz bandwidth. The whole system, combining these three modules, provides access to a THz spectrum peaking at 3.5 THz and extending beyond 6 THz with a maximum dynamic range of 50 dB for time-resolved spectroscopy applications. We demonstrate the functionality of this configuration by performing THz spectroscopy measurements of water vapor contained within a closed cell. Our compact system design paves the way towards a high-performance, yet cost-effective, THz-TDS system that can be readily used in academia and industry.