gebhart/patrepeval huggingface dataset:
TAK-994, a Novel Orally Available Brain-Penetrant Orexin 2 Receptor-Selective Agonist, Suppresses Fragmentation of Wakefulness and Cataplexy-Like Episodes in Mouse Models of Narcolepsy (2023)

Loss of orexin neurons is associated with narcolepsy type 1 (NT1), which is characterized by multiple symptoms including excessive daytime sleepiness and cataplexy. Orexin 2 receptor (OX2R) knockout (KO) mice, but not orexin 1 receptor (OX1R) KO mice, show narcolepsy-like phenotypes, thus OX2R agonists are potentially promising for treating NT1. In fact, in early proof-of-concept studies, intravenous infusion of danavorexton, an OX2R-selective agonist, significantly increased wakefulness in individuals with NT1. However, danavorexton has limited oral availability. Here, we report pharmacological characteristics of a novel OX2R agonist, TAK-994 [<i>N</i>-{(2<i>S</i>,3<i>S</i>)-1-(2-hydroxy-2-methylpropanoyl)-2-[(2,3',5'-trifluorobiphenyl-3-yl)methyl]pyrrolidin-3-yl}methanesulfonamide sesquihydrate]. TAK-994 activated recombinant human OX2R (EC<sub>50</sub> value of 19 nM) with > 700-fold selectivity against OX1R and activated OX2R-downstream signaling similar to those by orexin peptides in vitro. Oral administration of TAK-994 promoted wakefulness in normal mice but not in OX2R KO mice. TAK-994 also ameliorated narcolepsy-like symptoms in two mouse models of narcolepsy: orexin/ataxin-3 mice and orexin-tTA;TetO diphtheria toxin A mice. The wake-promoting effects of TAK-994 in orexin/ataxin-3 mice were maintained after chronic dosing for 14 days. These data suggest that overall in vitro and in vivo properties, except oral availability, are very similar between TAK-994 and danavorexton. Preclinical characteristics of TAK-994 shown here, together with upcoming clinical study results, can improve our understanding for orally available OX2R agonists as new therapeutic drugs for NT1 and other hypersomnia disorders. SIGNIFICANCE STATEMENT: Narcolepsy type 1 (NT1) is caused by a loss of orexin neurons, and thus an orexin 2 receptor (OX2R) agonist is considered to address the underlying pathophysiology of NT1. Oral administration of TAK-994, a novel OX2R agonist, promoted wakefulness in normal mice, but not in OX2R knockout mice, and ameliorated fragmentation of wakefulness and cataplexy-like episodes in mouse models of narcolepsy. These findings indicate that TAK-994 is an orally available brain-penetrant OX2R-selective agonist with potential to improve narcolepsy-like symptoms.
Reaction of .alpha.,.omega.-di-Grignard reagents with silver(I) salts forms carbocyclic rings (1976)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTReaction of .alpha.,.omega.-di-Grignard reagents with silver(I) salts forms carbocyclic ringsGeorge M. Whitesides and Francis D. GutowskiCite this: J. Org. Chem. 1976, 41, 17, 2882–2885Publication Date (Print):August 1, 1976Publication History Published online1 May 2002Published inissue 1 August 1976https://pubs.acs.org/doi/10.1021/jo00879a019https://doi.org/10.1021/jo00879a019research-articleACS PublicationsRequest reuse permissionsArticle Views773Altmetric-Citations50LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
Direct Bonding Technology by Chemical Reactions at the Interface and the Applications of Polyamide Elastomer (PEBA) (2010)

Regarding a bonding between conventional PEBA and TPU, it has following difficulties : (a) The PEBA which has less soft segment, i.e. harder PEBA is difficult to bond with TPU directly by Insert molding. (b) Overmolding TPU onto the inserted PEBA can not get a good bonding. Overmolding PEBA onto inserted TPU should be applied for a good bonding. (c) The bonding strength strongly depends on the chemical structure of the soft segment of TPU.Daicel-Evonik Ltd. had prepared several kinds of PEBAs based on the concept of the bonding by interfacial reactions for the bonding test with TPU and it was confirmed the concept could solve these problems of conventional PEBA. Additionally it was found that PEBA specimen as an insert was not influenced by a storage time before TPU’s overmolding, although TPU specimen lost its bonding performance by the time of the storage. This “PEBA insert system” was not available until Daicel-Evonik’s new PEBA and PA12. It is expected that these advantages of Daicel-Evonik’s new PEBA and PA12 will be able to contribute to new fine design, cost saving and stable mass production.These new PEBA and PA12 also can bond with rubber based on K&K concept. Rubber + new PEBA + TPU three layer sheet is introduced as one of the examples of new application.
Anatomy and Growth Characteristics of Conjugated Polyelectrolyte/DNA Aggregates (2008)

Abstract Conjugated polyelectrolytes (CPEs) have been widely used as light harvesting macromolecules to amplify the signals of fluorescent assays that betray the presence of various biomolecular targets. Electrostatic interactions play an important role in coordinating optical coupling events and lead to the formation of complexes between oppositely charged CPEs and the target species. Here, we combine for the first time optical studies and structural characterization by liquid phase atomic force microscopy (AFM) to provide a picture of aggregate structure and growth dynamics between cationic CPE and DNA as a function of charge ratio. Specifically, poly1 20 , a copolymer containing a backbone with 50% fluorene, 30% phenylene, and 20% 2,1,3‐benzothiadiazole (BT) units and pendant cationic groups was mixed with single stranded DNA (ssDNA) labeled with the Cy5 acceptor chromophore. Continuous addition of ssDNA‐Cy5 to poly1 20 leads to a saturation in Cy5 emission due to Cy5–Cy5 self‐quenching. Addition of ssDNA to a preformed poly1 20 /ssDNA‐Cy5 solution results in increased sensitization by energy transfer and a reduction of Cy5–Cy5 self quenching. Adsorption of aggregates onto negatively charged mica under water allows for direct imaging of the polyelectrolyte complexes as a function of charge ratio. The composite set of observations allows for the development of a model for aggregate growth, which is dynamic and ceases when the surface charge becomes sufficiently negative. This saturation point can be mitigated by addition of unlabeled ssDNA.
Enantiomeric Binding Elements Interacting at the Same Site of an SH3 Protein Receptor (1997)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTEnantiomeric Binding Elements Interacting at the Same Site of an SH3 Protein ReceptorSibo Feng and Stuart L. SchreiberView Author Information Department of Chemistry and Chemical Biology Howard Hughes Medical Institute, Harvard University Cambridge, Massachusetts 02138Cite this: J. Am. Chem. Soc. 1997, 119, 44, 10873–10874Publication Date (Web):November 5, 1997Publication History Received8 July 1997Published online5 November 1997Published inissue 1 November 1997https://pubs.acs.org/doi/10.1021/ja972255rhttps://doi.org/10.1021/ja972255rrapid-communicationACS PublicationsCopyright © 1997 American Chemical SocietyRequest reuse permissionsArticle Views145Altmetric-Citations9LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information SUBJECTS:Chemical structure,Elements,Ligands,Monomers,Receptors Get e-Alerts
Introduction to Sectional Anatomy Workbook and Board Review Guide (2007)

Introduction to Sectional Workbook and Board Review Guide helps you better understand the principles of sectional anatomy. When used in conjunction with its corresponding text, this workbook reinforces key concepts covered in Introduction to Sectional Anatomy and contains a variety of exercises and tools that make it easy for you to remember essential information and build critical-thinking skills. This resource is also designed to thoroughly prepare you for the CT and MR registry examinations.
Photoreflectance and photoinduced microwave reflectance studies of surface band bending in Mg-doped InN (2019)

Photoreflectance (PR) and microwave-reflectance photoconductivity-decay (μ-PCD) have been applied to study the surface band bending in Mg-doped InN layers with various Mg concentrations (∼1 × 1017 to ∼7 × 1019 cm−3) and thicknesses (∼400 to ∼3600 nm). A PR resonance related to the band-to-band transition at the Γ point below the surface electron accumulation is observed for moderately doped samples ([Mg]: 1.3 × 1017 cm−3 to 8.7 × 1017 cm−3). Samples with the Mg doping concentration in the range of ∼5 × 1018 ≤ [Mg] ≤ 7 × 1019 cm−3 are p-type and show very weak or no PR resonance. It is shown that the results correlate with the surface layer depletion thickness. The strongest PR signal is observed for thick depletion layers. The results are confirmed by μ-PCD measurements that show the longest carrier lifetimes for moderately doped samples with the thickest surface depletion layer.
Techniques for achieving low leakage current in dry etched InGaAs waveguide PIN detectors (2004)

InGaAs waveguide PIN detectors require a low leakage current and adequate passivation. Removing dry-etch-induced subsurface damage and surface residues on mesa sidewalls prior to passivation is not only important in reducing these leakage currents, but it is also critical in preventing device degradation. In this article, we investigate the effects of the mesa sidewall clean treatment on the InGaAs waveguide PINs etched using a methane-based (CH4) reactive ion etch (RIE) and a hydrogen bromide-based (HBr) inductively coupled plasma etch (ICP). Post-dry-etching treatments have been developed employing a rapid thermal anneal, followed by a series of Br-, H2SO4-, and HF-based cleaning processes. Transmission electron microscopy analysis shows no apparent sidewall damage, which could cause high leakage currents. Scanning electron microscopy shows sidewall etch by-product removal and ridge CD maintenance after the wet cleaning processes. Very low leakage currents, comparable to those observed in damage-free wet-etched waveguides, were achieved using the RIE or ICP etches, followed by the combination of post dry-etch treatments. I-V measurements were used to provide a quick feedback of sidewall quality and a sensitive method for evaluating the level of damage in these devices as compared to other analytical techniques.
Semiconductor-based low-noise 100 MHz chirped pulse laser source based on a theta cavity design with an intra-cavity etalon and long-term stabilization (2011)

This work discusses the development of a frequency chirped, low repetition rate, semiconductor based mode-locked laser having reduced noise over previous demonstrations. Specifically, we present a major upgrade on the 100 MHz harmonically mode-locked Theta (&#920;) laser cavity design in the form of the introduction of an intra-cavity fiberized Fabry-Perot etalon. The initial demonstration of the Theta cavity design offered improved energy per pulse and a linearly chirped pulse output compared to conventional cavity designs. Nonetheless, it suffered from pulse-to-pulse timing and energy noise. The noisy operation arises from the harmonic nature of the laser. To mitigate this effect we have inserted a fiberized etalon within the laser cavity. The intra-cavity etalon stores and inter-mixes the pulses of the harmonically mode-locked laser, as well as enforces lasing on a single optical mode-set from the multiple interleaved sets supported by the mode-locked laser due to its harmonic nature. This leads to the generation of a stable optical frequency comb with 100 MHz spacing and the suppression of the RF super-mode noise spurs, which results in a reduction of the laser noise. Due to fiber length drift in both the fiberized laser cavity and the fiberized etalon, a long-term stabilization scheme is necessary. An intra-cavity Hansch - Couillaud scheme is employed. The laser outputs chirped pulses with 10 nm of bandwidth. This work provides an in depth analysis of both the development of the Theta cavity with the intra-cavity etalon and the performance of the developed laser system.
Computational Light Routing: 3D Printed Optical Fibers for Sensing and Display (2014)

Despite recent interest in digital fabrication, there are still few algorithms that provide control over how light propagates inside a solid object. Existing methods either work only on the surface or restrict themselves to light diffusion in volumes. We use multi-material 3D printing to fabricate objects with embedded optical fibers, exploiting total internal reflection to guide light inside an object. We introduce automatic fiber design algorithms together with new manufacturing techniques to route light between two arbitrary surfaces. Our implicit algorithm optimizes light transmission by minimizing fiber curvature and maximizing fiber separation while respecting constraints such as fiber arrival angle. We also discuss the influence of different printable materials and fiber geometry on light propagation in the volume and the light angular distribution when exiting the fiber. Our methods enable new applications such as surface displays of arbitrary shape, touch-based painting of surfaces, and sensing a hemispherical light distribution in a single shot.
The Molecular Basis for the Relationship between the Secondary Relaxation and Mechanical Properties of a Series of Polyester Copolymer Glasses (1999)

A correlation between the yield behavior of copolymers based on poly(ethylene terephthalate) and poly(1,4-cyclohexylenedimethylene terephthalate) (PCT) and their secondary relaxation motions is established. The yield stress decreases as the cyclohexylene content increases for different temperatures and strain rates. The activation volume based on Eyring's model of yielding increases as the copolymers become more PCT-like, while the activation energy does not exhibit any significant change. We speculate that the conformational changes of the cyclohexylene rings reduce the barriers between chain segments sufficiently to facilitate chain slippage. This is supported by the increased dynamic fluctuation found by positron annihilation lifetime spectroscopy. The crazing stress of the copolyesters increases with increasing cyclohexylene content. We propose that the formation of stable microvoids is impeded by local stress relaxation; hence craze formation is retarded. The ductile/brittle transition is viewed as a competition between yielding and crazing with changes in the transition temperature dependent on activation of molecular motions of the cyclohexylene groups.
Quad Precision Floating Point on the IBM z13 (2016)

When operating on a rapidly increasing amount of data, business analytics applications become sensitive to rounding errors, and profit from the higher stability and faster convergence of quad precision floating-point (FP-QP) arithmetic. The IBM z13 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">TM</sup> supports this emerging trend around Big Data with an outstanding FP-QP performance. The paper details the vector and floating-point unit of IBM z13 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">TM</sup> , with special focus on binary FP-QP. Except for divide and square root, these instructions are executed in the decimal engine. To operate such an 8-cycle decimal and quad precision pipeline at 5GHz required innovation around exponent handling, normalization, and rounding.
ChemInform Abstract: A New Rigid Benzene‐Bridged Macrotricyclic Ligand (2001)

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.
Study of Immersion of LiNi0.5Mn0.3Co0.2O2 Material in Water for Aqueous Processing of Positive Electrode for Li-Ion Batteries (2019)

The understanding of the phenomena occurring during immersion of LiNi<sub>0.5</sub>Mn<sub>0.3</sub>Co<sub>0.2</sub>O<sub>2</sub> (NMC) in water is helpful to devise new strategies toward the implementation of aqueous processing of this high-capacity cathode material. Immersion of NMC powder in water leads to both structural modification of the particles surface as observed by high-resolution scanning transmission electron microscopy and the formation of lithium-based compounds over the surface (LiOH, Li<sub>2</sub>CO<sub>3</sub>) in greater amount than after long-time exposure to ambient air, as confirmed by pH titration and <sup>7</sup>Li MAS NMR analysis. The surface compounds adversely affect the electrochemical performance and are notably responsible for the alkaline pH of the aqueous slurry, which causes corrosion of the aluminum collector during coating of the electrode. The corrosion is avoided by adding phosphoric acid to the slurry as it lowers the pH, and it also enhances the cycling stability of the water-based electrodes due to the phosphate compounds formed at the particles surface, as evidenced by X-ray photoelectron spectroscopy analysis.
ChemInform Abstract: Synthesis of a Dithia‐18‐crown‐6‐tetracarboxylic Acid. (1986)

Abstract Aus dem optisch aktiven Weinsäurediamid (Ia) werden in üblicher Weise die Derivate (Ib)‐(Ig) hergestellt.
Research highlights: increasing paper possibilities (2014)

In this issue we highlight three recent papers that demonstrate new strategies to extend the capabilities of paper microfluidics. Paper (a mesh of porous fibers) has a long history as a substrate to perform biomolecular assays. Traditional lateral flow immunoassays (LFAs) are widely used for rapid diagnostic tests, and perform well when a yes or no answer is required and the analyte of interest is at relatively high concentrations. High concentrations are required because usually only a small volume of analyte-containing fluid flows past the detection region, leading to a limited signal. Further, the small pores within paper matrices prevent the use of paper to control the flow of larger particles and cells, limiting the use of paper microfluidics for cell-based diagnostics. The work we highlight addresses these important unmet challenges in paper microfluidics: enriching low concentration analytes to a higher concentration in a smaller volume that can be processed effectively, and using paper to pump flows in larger channels amenable to cells. Applying these new approaches may allow diagnosis of disease states currently technically unachievable using current LFA systems, while maintaining many of the "un-instrumented" advantages of an assay on self-wicking paper.
Enhanced Performance of Alkali Metal Doped Fe2O3 and Fe2O3/Al2O3 Composites As Oxygen Carrier Material in Chemical Looping Combustion (2013)

In this study alkali metal doped Fe2O3 and Fe2O3/Al2O3 composite oxygen carriers were synthesized from spray pyrolysis, and the reactivity and stability as oxygen carrier materials were evaluated in a fixed bed reactor for 50 isothermal redox cycles using CH4 as the fuel. We find that both Fe2O3 and Fe2O3/Al2O3 composite showed reactivity degradation over multiple cycles, with a clear phase separation between Fe and Al, in the composites. In contrast, alkali metal doping (∼5 mol %) with Na, K, and Cs was found to stabilize the reactivity of the Fe2O3 over the 50 redox cycles and prevent phase Fe–Al separation in the composite. Methane to CO2 selectivity was found to be relevant to the dopant type, which decreased in the order of dopant type K, Cs, and Na. The best performing alkali metal, K, enhanced long-term stability significantly, with no observed degradation in kinetics and total conversion performance in the methane step as well as reduced coke formation. Adding an alumina matrix to K doped Fe2O3 helped promote CO2 generation as well as minimize coking and was found to be the best performing material.
Spatio-temporal dynamics of the resonantly excited relativistic plasma wave driven by a CO2 laser (1997)

The dynamics of a relativistic plasma wave (RPW) resonantly excited by a two frequency CO2 laser pulse and the effects of this wave on a co-propagating relativistic electron beam were studied through experiments and supporting simulations. The amplitude of the RPW and its harmonics were resolved in time and space with a Thomson scattering diagnostic. In addition, the plasma wave amplitude-length product and temporal duration were independently measured through time and frequency resolved forward scattering. The transverse electric and magnetic fields associated with the RPW were studied by the scattering of a 2 MeV electron beam, and the eventual heating of the plasma after the breakup of the RPW was measured from the x-ray radiation spectrum. The experiments and simulations show that the RPW reaches a peak amplitude of approximately 30%, with the amplitude limited by plasma blowout driven by the radial ponderomotive forces of the plasma wave.
Rapid modulation of local neural activity by controlled drug release from polymer-coated recording microelectrodes (2011)

We demonstrate targeted perturbation of neuronal activity with controlled release of neurochemicals from conducting polymer-coated microelectrodes. Polymer coating and chemical incorporation are achieved through individually addressable electrodeposition, a process that does not compromise the recording capabilities of the electrodes. Release is realized by the application of brief voltage pulses that electrochemically reduce the polymer and dissociate incorporated neurochemicals; whereby they can diffuse away and achieve locally effective concentrations. Inhibition of evoked synaptic currents in neurons within 200 µm of a 6-cyano-7-nitroquinoxaline-2,3-dione releasing electrode lasts for several seconds. Spiking activity of neurons in local circuits recorded extracellularly near the releasing electrode is silenced for a similar duration following release. This methodology is compatible with many neuromodulatory chemicals and various recording electrodes, including in vitro and implantable neural electrode arrays, thus providing an inexpensive and accessible technique capable of achieving sophisticated patterned chemical modulation of neuronal circuits.