gebhart/patrepeval huggingface dataset:
Metal Ion Separations in Aqueous Biphasic Systems and Using Aqueous Biphasic Extraction Chromatography (1999)

Polyethylene glycol-based aqueous biphasic systems (ABS) and the complementary aqueous biphasic extraction chromatographic (ABEC) resins are capable of selectively removing metal ions from complex solutions, such as the radioactive Hanford tank waste supernates. These aqueous separations methods have the potential to eliminate the use of volatile organic solvents in many separations, yet their utility in more conventional solvent extraction processes has until recently received scant attention. This paper reviews the nature of ABS and ABEC separations, categorizes the types of possible metal ion separations, and discusses where these techniques may find practical application. The relationship between the liquid/liquid ABS separations and the chromatographic ABEC separations is discussed in detail.
The effect of synthetic retinoid, Am80, on T helper cell development and antibody production in murine collagen-induced arthritis (2009)

Retinoids are known to promote T helper (Th)2 and regulatory T cell (Treg) differentiation, and suppress Th1 and Th17 in vitro. Am80, a synthetic retinoid, is reported to ameliorate collagen-induced arthritis (CIA). The aims of this study are to determine the effects of Am80 on CIA in detail, and on Th development and antibody (Ab) production in vivo. Murine CIA was induced by immunization with bovine type II collagen (CII) at days 1 and 22. Treatment with Am80 from day 1 to 35 significantly lowered clinical arthritis score, suppressed cellular infiltration and bone destruction in the joint, decreased interleukin (IL)-17 and increased interferon (IFN)-gamma production by CII-stimulated splenocytes, and decreased proportion of Foxp3(+) splenic CD4 T cells and serum anti-CII Ab levels. Thus, Am80 inhibited Th17 and Treg and enhanced Th1 differentiation in vivo. In contrast, Am80 applied from day 15 to 35 did not alter arthritis score, IL-17 or IFN-gamma production by CII-stimulated splenocytes, but decreased the proportion of Foxp3(+) splenic CD4 T cells and serum anti-CII Ab levels. Am80 exhibits inhibitory effects on CIA and might regulate both Th development and Ab production in vivo. Decreased Th17 by treatment with Am80 might be responsible for the attenuation of arthritis.
MRI features of benign multiple sclerosis (2009)

It is well known that the current classification of patients with benign multiple sclerosis (BMS), i.e., those with absent or minimal locomotor disability several years after disease onset, suffers from not having any prognostic value for the subsequent evolution of multiple sclerosis (MS). The identification of markers predictive of the longer-term course of MS will help define BMS more reliably and would allow better counseling of patients, particularly when advising on the initiation of a disease-modifying treatment. MRI-based evidence suggests that there are three potential, but not mutually exclusive, explanations for the scarce clinical impact of BMS: 1) the paucity of tissue damage within and outside MS lesions; 2) the relative sparing of clinically eloquent regions; and 3) the presence of effective compensatory mechanisms. In addition, the results of correlative MRI/neuropsychology studies underpin the need for a new definition of BMS, which should consider the maintenance of a normal cognitive profile as an additional criterion.
Transfer of Chirality in Radical Cyclizations. Cyclization of o-Haloacrylanilides to Oxindoles with Transfer of Axial Chirality to a Newly Formed Stereocenter (1999)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTTransfer of Chirality in Radical Cyclizations. Cyclization of o-Haloacrylanilides to Oxindoles with Transfer of Axial Chirality to a Newly Formed StereocenterDennis P. Curran, Weidong Liu, and Christine Hiu-Tung ChenView Author Information Department of Chemistry, University of Pittsburgh Pittsburgh, Pennsylvania 15260 Cite this: J. Am. Chem. Soc. 1999, 121, 47, 11012–11013Publication Date (Web):November 11, 1999Publication History Received14 September 1999Published online11 November 1999Published inissue 1 December 1999https://pubs.acs.org/doi/10.1021/ja993329xhttps://doi.org/10.1021/ja993329xrapid-communicationACS PublicationsCopyright © 1999 American Chemical SocietyRequest reuse permissionsArticle Views1484Altmetric-Citations95LEARN 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:Chirality,Cyclization,Molecular structure,Organic reactions,Precursors Get e-Alerts
Conductive dots, wires, and supertips for field electron emitters produced by electron-beam induced deposition on samples having increased temperature (1996)

The procedure for three-dimensional additive lithography with electron-beam induced deposition is applied in a scanning electron microscope equipped with an image processor beam control system for lithography. Employing organometallic materials, which contain gold or platinum, quantum dots, resistors, and field emitter tips are deposited. Changing the current, the properties of the deposited nanocrystalline compound materials can be selected to be insulating or conducting. High resolution and high aspect ratio structures are grown with this technique. To find the mechanism responsible for conductivity in the deposited material, resistors are characterized at temperatures ranging from −150 °C to +180 °C. Measurements are performed in a high-vacuum chamber equipped with a gas cooling system cooled with liquid nitrogen and a resistive heater. Poole–Frenkel plots show that field electron emission and hopping of electrons is the dominant mechanism of conduction. The metal content of the deposits is increased with rising sample temperatures ranging from room temperature to 100 °C. The deposited material features zero-dimensional electron gas in the nanocrystals of the material. Conductive tips with very small tip radius are routinely deposited as supertips on top of etched tungsten tips at elevated temperatures. The tips are investigated in an ultrahigh vacuum field electron microscope. Working supertips have a confined emission and therefore enhanced brightness is obtained routinely. The increase in brightness is at least ninefold for an emission from one site having a confined emission angle of ±7.2°. The emission current may be as large as 10 μA at extraction voltages below 800 V. No single crystalline tip material is needed to generate these supertips. Beam confinement to one emission site is demonstrated the first time for a deposited supertip.
Safety Guarantees for Iterative Predictions with Gaussian Processes (2020)

Gaussian Processes (GPs) are widely employed in control and learning because of their principled treatment of uncertainty.<br> However, tracking uncertainty for iterative, multi-step predictions in general leads to an analytically intractable problem.<br> While approximation methods exist, they do not come with guarantees, making it difficult to estimate their reliability and to trust their predictions.<br> In this work, we derive formal probability error bounds for iterative predictions with GPs.<br> Building on GP properties, we bound the probability that random trajectories lie in specific regions around the predicted values.<br> Namely, given a tolerance $\epsilon &gt; 0 $, we compute regions around the predicted trajectory values, such that GP trajectories are guaranteed to lie inside them with probability at least $1-\epsilon$.<br> We verify experimentally that our method tracks the predictive uncertainty correctly, even when current approximation techniques fail.<br> Furthermore, we show how the proposed bounds can incorporate a given control law, and effectively bound the trajectories of the closed-loop system.
Directional Equalization of Sparse Head-Related Transfer Function Sets for Spatial Upsampling (2019)

Acquiring decent full-spherical sets of head-related transfer functions (HRTFs) based on a small number of measurements is highly desirable. For spatial upsampling, HRTF interpolation in the spatially continuous spherical harmonics (SH) domain is a common approach. However, the number of measured HRTFs limits the assessable SH order, resulting in order-limited HRTFs when transformed to the SH domain. Thus, the SH representation of sparse HRTF sets shows restricted spatial resolution and suffers from order-limitation errors. We present a method that reduces these errors by a directional equalization prior to the SH transform. This is done by a spectral division of each HRTF with a corresponding directional rigid sphere transfer function. The processing removes direction-dependent temporal and spectral components and, therefore, significantly reduces the spatial complexity of the HRTF set, allowing for an enhanced interpolation of HRTFs at reduced SH orders. Spatial upsampling is achieved by an inverse SH transform on an arbitrary dense sampling grid. A subsequent de-equalization by a spectral multiplication with the rigid sphere transfer function recovers the energy in higher spatial orders that was not inherent in the sparse HRTF set. For evaluation, HRTFs were calculated for various limited orders from sparse datasets and compared to a reference. The results show that the proposed method clearly outperforms common SH interpolation of HRTF spectra regarding the overall spectral and temporal structure as well as modeled localization performance.
Nanocrystal hybridized scintillators for enhanced detection and imaging on Si platforms in UV (2007)

We report on the conception, design, fabrication, experimental characterization, and theoretical analysis of nanocrystal scintillators hybridized on Si detectors and CCDs for enhanced detection and imaging in UV. Integrating luminescent CdSe/ZnS core-shell nanocrystals (NCs of 3.2 and 5.2 nm in diameter with 5% size distribution) to efficiently convert incident UV radiation to visible emission, we demonstrate hybrid NC-Si photodetectors that exhibit significantly improved responsivity between 200-240nm, experimentally with a two orders of magnitude peak enhancement and theoretically with a three orders of magnitude peak enhancement. Such nanocrystal based scintillators hold great promise in UV detection and imaging on Si platforms.
Phototoxic effects of lysosome-associated genetically encoded photosensitizer KillerRed (2013)

KillerRed is a unique phototoxic red fluorescent protein that can be used to induce local oxidative stress by green-orange light illumination. Here we studied phototoxicity of KillerRed targeted to cytoplasmic surface of lysosomes via fusion with Rab7, a small GTPase that is known to be attached to membranes of late endosomes and lysosomes. It was found that lysosome-associated KillerRed ensures efficient light-induced cell death similar to previously reported mitochondria- and plasma membrane-localized KillerRed. Inhibitory analysis demonstrated that lysosomal cathepsins play an important role in the manifestation of KillerRed-Rab7 phototoxicity. Time-lapse monitoring of cell morphology, membrane integrity, and nuclei shape allowed us to conclude that KillerRed-Rab7-mediated cell death occurs via necrosis at high light intensity or via apoptosis at lower light intensity. Potentially, KillerRed-Rab7 can be used as an optogenetic tool to direct target cell populations to either apoptosis or necrosis.
Planning for NATO's nuclear deterrent in the 1980s and 1990s (1983)

Abstract : NATO planners need to look anew at: the structure of short- and medium-range theater nuclear forces, the contribution that U.S. sea-based and intercontinental nuclear assets make to NATO's deterrent, NATO's capabilities to direct its forces in war, and the size of the nuclear stockpile in Europe. Notwithstanding their potential for political controversy, a comprehensive examination of these issues should not be delayed very much longer. Although the strategy is indeed vague, planning for NATO's nuclear deterrent forces does not necessarily have to proceed bereft of direction. A framework for planning can be constructed on the basis of the flexible response strategy, especially if NATO planners take careful account fo developments that have occurred since its adoption in 1967.
The Role of Positron Emission Tomography and Computed Tomography Fusion in the Management of Early-Stage and Advanced-Stage Primary Head and Neck Squamous Cell Carcinoma (2006)

The use of PET-CT is important in the initial treatment planning of early-stage and advanced-stage head and neck squamous cell carcinoma.
Small molecule transcriptional activation domains (2008)

Transcriptional activators are essential for high fidelity transcription, responsible for seeking out particular genes and up-regulating them to precise levels in a signal responsive fashion. Indeed the altered transcription patterns observed in disease states can often be attributed to malfunctioning and/or misregulated transcriptional activators. Thus, molecules that can reconstitute the function of transcriptional activators, artificial transcription activators, are highly desirable commodities as mechanistic tools and transcription-targeted therapeutics. Transcriptional activators control the specificity and extent of gene upregulation through two domains: the DNA binding domain (DBD) is responsible for the former and the transcriptional activation domain (TAD) dictates the level of gene expression. It has proven quite challenging to identify TAD replacements with functional properties comparable to the natural system despite their likely advantages in terms of stability, delivery, and and/or immunogenic properties. This is likely due to the many open questions surrounding how natural transcriptional activation domains function. To address the need for the development and characterization of small molecule TADs we have employed a combination of organic chemistry, NMR spectroscopy, and biological evaluations to a class of isoxazolidines that functionally mimic natural TADs. We prepared five stereochemically pure isoxazolidine isomers, each of which contained identical functional groups (benzyl, isobutyl and hydroxyl) arranged in different positions around the isoxazolidine ring. All of these amphipathic isoxazolidines functioned as TADs in a cell-free assay, revealing that analogous to endogenous TADs, a particular positioning of functional groups is not required for transcription function. Similar functional trends were observed in a cellular assay. We further demonstrated that the small molecule TADs interact with at least a subset of the same coactivator proteins as do natural TADs. In particular, interaction with the KIX domain of Creb Binding Protein is correlated with transcription function, although binding interactions with Tra1, Med15 and Med23 are also observed. These molecules are thus anticipated to be an excellent starting point for the design of more potent small molecule regulators of transcription.
In-line ultrasonic monitoring of waste slurry suspended solids (2000)

During the transport of tank waste, it is very important to quantitatively measure the percent solids concentration (PSC) of the waste, which indicates the flow conditions and the extent of solids settling. At Argonne National Laboratory, an in-line, real-time, a nonintrusive ultrasonic monitoring system has been developed to measure the PSC and flow density of tank waste by measuring sound velocity and attenuation in the flow. This system consists of a pair of longitudinal transducers bonded to waveguides on the opposite sides of the pipe and operating at IMHz simultaneously in pulse-and-echo and pitch-and-catch modes. The PSC measurement is provided by attenuation, while the density measurement is calculated by impedance and sound velocity. A thermocouple is attached to one of the waveguides for automatic temperature correction of the measurements. This system was one of four evaluated for in-line measurement of slurry at Oak Ridge National Laboratory in 1998. The results indicate that the measurements are in good agreement with a Coriolis meter and that the system can be used to monitor PSC up to 40 wt.%. However, the system is greatly affected by entrained air bubbles within the solid flow during Puisair mixing. A different mixing mechanism will solve this problem.
Mixed Meal Simulation Model of Glucose-Insulin System (2006)

A simulation model of the glucose-insulin system in the postprandial state can be useful for studying the pathophysiology of diabetes. Here we present a new simulation model which describes the physiological events which occur after a meal, by employing the quantitative knowledge which has become available in recent years. Model parameters were set to fit data of 204 normal subjects which underwent a triple tracer meal protocol which provided quasi model-independent estimates of major glucose and insulin fluxes. Model results are shown in describing normal daily life (breakfast, lunch, dinner) both in normal and pathophysiological situations. The potential of the model for studying type 1 diabetes is illustrated by simulating both open- and closed-loop insulin infusion strategies
Development of an Amorphous Solid Dispersion Formulation for Mitigating Mechanical Instability of Crystalline Form and Improving Bioavailability for Early Phase Clinical Studies (2023)

In this work, an amorphous solid dispersion (ASD) formulation was systematically developed to simultaneously enhance bioavailability and mitigate the mechanical instability risk of the selected crystalline form of a development drug candidate, GDC-0334. The amorphous solubility advantage calculation was applied to understand the solubility enhancement potential by an amorphous formulation for GDC-0334, which showed 2.7 times theoretical amorphous solubility advantage. This agreed reasonably well with the experimental solubility ratio between amorphous GDC-0334 and its crystalline counterpart (∼2 times) in buffers of a wide pH range. Guided by the amorphous solubility advantage, ASD screening was then carried out, focusing on supersaturation maintenance and dissolution performance. It was found that although the type of polymer carrier did not impact ASD performance, the addition of 5% (w/w) sodium dodecyl sulfate (SDS) significantly improved the GDC-0334 ASD dissolution rate. After ASD composition screening, stability studies were conducted on selected ASD powders and their hypothetical tablet formulations. Excellent stability of the selected ASD prototypes with or without tablet excipients was observed. Subsequently, ASD tablets were prepared, followed by <i>in vitro</i> and <i>in vivo</i> evaluations. Similar to the effect of facilitating the dissolution of ASD powders, the added SDS improved the disintegration and dissolution of ASD tablets. Finally, a dog pharmacokinetic study confirmed 1.8 to 2.5-fold enhancement of exposure by the developed ASD tablet over the GDC-0334 crystalline form, consistent with the amorphous solubility advantage of GDC-0334. A workflow of developing an ASD formulation for actual pharmaceutical application was proposed according to the practice of this work, which could provide potential guidance for ASD formulation development in general for other new chemical entities.
Highly Sensitive Raman Spectroscopy with Low Laser Power for Fast In-Line Reaction and Multiphase Flow Monitoring (2016)

In process analytics, the applicability of Raman spectroscopy is restricted by high excitation intensities or the long integration times required. In this work, a novel Raman system was developed to minimize photon flux losses. It allows specific reduction of spectral resolution to enable the use of Raman spectroscopy for real-time analytics when strongly increased sensitivity is required. The performance potential of the optical setup was demonstrated in two exemplary applications: First, a fast exothermic reaction (Michael addition) was monitored with backscattering fiber optics under strongly attenuated laser power (7 mW). Second, high-speed scanning of a segmented multiphase flow (water/toluene) with submicroliter droplets was achieved by aligning the focus of a coaxial Raman probe with long focal length directly into a perfluoroalkoxy (PFA) capillary. With an acquisition rate of 333 Raman spectra per second, chemical information was obtained separately for both of the rapidly alternating phases. The experiment with reduced laser power demonstrates that the technique described in this paper is applicable in chemical production processes, especially in hazardous environments. Further potential uses can be envisioned in medical or biological applications with limited power input. The realization of high-speed measurements shows new possibilities for analysis of heterogeneous phase systems and of fast reactions or processes.
Constrained catecholamines gain β2AR selectivity through allosteric effects on pocket dynamics (2023)

G protein-coupled receptors (GPCRs) within the same subfamily often share high homology in their orthosteric pocket and therefore pose challenges to drug development. The amino acids that form the orthosteric binding pocket for epinephrine and norepinephrine in the β<sub>1</sub> and β<sub>2</sub> adrenergic receptors (β<sub>1</sub>AR and β<sub>2</sub>AR) are identical. Here, to examine the effect of conformational restriction on ligand binding kinetics, we synthesized a constrained form of epinephrine. Surprisingly, the constrained epinephrine exhibits over 100-fold selectivity for the β<sub>2</sub>AR over the β<sub>1</sub>AR. We provide evidence that the selectivity may be due to reduced ligand flexibility that enhances the association rate for the β<sub>2</sub>AR, as well as a less stable binding pocket for constrained epinephrine in the β<sub>1</sub>AR. The differences in the amino acid sequence of the extracellular vestibule of the β<sub>1</sub>AR allosterically alter the shape and stability of the binding pocket, resulting in a marked difference in affinity compared to the β<sub>2</sub>AR. These studies suggest that for receptors containing identical binding pocket residues, the binding selectivity may be influenced in an allosteric manner by surrounding residues, like those of the extracellular loops (ECLs) that form the vestibule. Exploiting these allosteric influences may facilitate the development of more subtype-selective ligands for GPCRs.
MICROFLUIDIC DARWINIAN EVOLUTION (2008)

Directed evolution is the application of Darwinian principles to populations of molecules. Repeated rounds of selection, mutagenesis, and amplification yield macromolecules with desired chemical functions. Conventional approaches are necessarily ad hoc, relegating the control of experimental parameters such as selection pressure and mutagenesis to guesswork. We have constructed the first chip-based system that interfaces computer control with Darwinian evolution to eliminate manual sample manipulation and to provide real-time feedback describing evolutionary progress.