gebhart/patrepeval huggingface dataset:
Identification of Novel Inhibitors of M. tuberculosis Growth Using Whole Cell Based High-Throughput Screening (2012)

Despite the urgent need for new antitubercular drugs, few are on the horizon. To combat the problem of emerging drug resistance, structurally unique chemical entities that inhibit new targets will be required. Here we describe our investigations using whole cell screening of a diverse collection of small molecules as a methodology for identifying novel inhibitors that target new pathways for Mycobacterium tuberculosis drug discovery. We find that conducting primary screens using model mycobacterial species may limit the potential for identifying new inhibitors with efficacy against M. tuberculosis. In addition, we confirm the importance of developing in vitro assay conditions that are reflective of in vivo biology for maximizing the proportion of hits from whole cell screening that are likely to have activity in vivo. Finally, we describe the identification and characterization of two novel inhibitors that target steps in M. tuberculosis cell wall biosynthesis. The first is a novel benzimidazole that targets mycobacterial membrane protein large 3 (MmpL3), a proposed transporter for cell wall mycolic acids. The second is a nitro-triazole that inhibits decaprenylphosphoryl-β-D-ribose 2'-epimerase (DprE1), an epimerase required for cell wall biosynthesis. These proteins are both among the small number of new targets that have been identified by forward chemical genetics using resistance generation coupled with genome sequencing. This suggests that methodologies currently employed for screening and target identification may lead to a bias in target discovery and that alternative methods should be explored.
Single-Core PAHs in Petroleum- and Coal-Derived Asphaltenes: Size and Distribution from Solid-State NMR Spectroscopy and Optical Absorption Measurements (2016)

Using solid-state 13C NMR spectroscopy of two different asphaltenes, one derived from petroleum and the other from coal liquids, it was shown that the asphaltene molecular architecture consists of a spectrum of sizes, ranging from smaller polyaromatic hydrocarbons (PAHs; <5 condensed rings) to much larger ones (>9 condensed rings), but their distribution varies between the two. It is shown that smaller PAHs are likely more abundant in the coal-derived asphaltenes, while the largest PAH cores of the two different asphaltenes are similar in size. These observations are reinforced by optical absorption. The coal-derived asphaltenes were found to contain a small fraction of archipelago-type structures, where a small PAH is tethered to the larger PAH core via an aryl linkage, which are less evident, and likely less abundant, in the petroleum asphaltenes. An important difference between the two asphaltenes lies in their alkyl fraction, with the petroleum asphaltenes possessing significantly longer and more mobile alkyl side chains, on average ∼7 carbons long, as opposed to an average chain length of ∼3–4 in the coal asphaltenes. The petroleum asphaltenes also possess a larger fraction of alicyclics. The longer length increases the propensity of the petroleum asphaltene alkyl side chains to intercalate between the aromatic rings of adjacent asphaltene aggregates, which is not observed in coal-derived asphaltenes. This work demonstrates the utility of combining cross-polarization dynamics and directly polarized 13C solid-state NMR spectroscopy in studying asphaltenes, while adding to the body of evidence supporting the single-core model of asphaltenes, which appears to be the dominant structural motif for this fraction of petroleum.
Analysis of the loss from a human hand for the reduction of spatial losses (2011)

The total radiated power is one of the most important factor for designing a mobile handset. Thus, in this work, a spatial loss which comes from a human hand was studied to find an effective way to reduce losses and increase the radiated power. A simple lossy object and a half-wavelength dipole antenna were used for the analysis to find a basic principle of the generation of electric fields inside a human hand. From the results, it was verified that there are internal resonance modes in which the electric field and the loss are maximized, and the resonance depends on the shape and size of a lossy object. Therefore, it must be possible to reduce the loss from a human hand by designing the handset antenna to avoid the resonant mode.
Novel refreshable N‐halamine polymeric biocides containing imidazolidin‐4‐one derivatives (2001)

Abstract A novel cyclic‐amine monomer, 1‐acryloyl‐2,2,5,5‐tetramethylimidazolidin‐4‐one (ACTMIO), was synthesized in a good yield through the reaction of acryloyl chloride with 2,2,5,5‐tetramethylimidazolidin‐4‐one and was fully characterized with Fourier transform infrared and 1 H NMR studies. ACTMIO was copolymerized with several widely used acrylic and vinyl monomers under ordinary conditions. In the presence of triallyl‐1,3,5‐triazine‐2,4,6(1H,3H,5H)‐trione, ACTMIO was easily grafted onto most textile fabrics. After regular chlorine bleach treatment, N ‐halamine derivatives of the corresponding polymeric materials exhibited antibacterial properties against Escherichia coli , and these properties were durable and refreshable with chlorine bleaching. The relationship between the structures and antibacterial properties of the samples is further discussed. © 2001 John Wiley &amp; Sons, Inc. J Polym Sci Part A: Polym Chem 39: 3073–3084, 2001
Studies on Arthropoda (1921)

A. Sub-order Amblypy$ési.In his monograph (Revision der Tarentuliden Fabr., 1895) K. Kraepelin accepted three sub-families, and in 1902 R. I. Pocock elevated them to the rank of families.Only one of these families, viz. the Phrynidee, was hitherto known from Africa, and a single well-known form is represented in the collection.But this contains besides two species of the family Charontide, which hitherto was known only from the Indo-Australian region and the Galapagos Islands.It may be inserted that I am inclined to consider the second of the two long joints in the mandibular palps as corresponding to patella plus tibia in Aranez and Pedipalpi Uropygi; in the descriptions I can therefore follow Kraepelin who named it tibia.Titanodamon medius Herbst.Kraepelin mentioned three varieties, viz.typicus Kraep., tibialis Simon, and Johnstoni Pocock; the two last-named varieties had been established as separate species
New Waveforms for 5G Networks [Guest editor introduction] (2016)

The articles in this special section focus on new waveform technologies and services for 5G mobile communications.
Uterine Artery Embolization of Symptomatic Leiomyomata: Observations on Our Initial Experience at Georgetown University Medical Center (2000)

Since the start of our uterine fibroid embolization (UFE) program at Georgetown University Medical Center, our approach to patient selection, procedure techniques, and postprocedure care has evolved. In this article, we summarize our current protocol for UFE and the rationale for our approach. Many of the technical issues associated with UFE are as yet unsettled, and we hope to stimulate others to present their approach. We describe some of the pitfalls associated with measuring outcome for the procedure. We conclude with our perspective on the remaining research issues that require further study.
Interrelationships of polymorphonuclear neutrophil membrane-bound calcium, membrane potential, and chemiluminescence: studies in single living cells (1984)

Stimulated neutrophils show ionic fluxes that may function as "transducers" between stimuli and effector functions. Using fluorescent probes, patterns of membrane-associated calcium (chlortetracycline, CTC) and membrane potential (3-3'-dipentyloxacarbocyanine, di-O-C5 (3)) in single living human neutrophils were observed with a fluorescence microscope fitted with an image intensifier and photometer. Fluorescence changes were related to chemiluminescence. In unstimulated neutrophils, CTC and di-O-C5 (3) fluorescence was brightest in the perinuclear region. Di-O-C5 (3) fluorescence was also seen in mitochondria. Neutrophil stimulation with zymosan, phorbol myristate acetate (PMA) or calcium ionophore (A23187) resulted in loss of di-O-C5 (3) and CTC fluorescence and chemiluminescence proportional to the strength of the stimulus. Experiments demonstrated the independence of these processes. (1) Digitonin stimulation caused chemiluminescence and di-O-C5 (3) darkening without loss of CTC fluorescence. (2) Depolarization of neutrophils did not induce CTC darkening or chemiluminescence. (3) Calcium ionophore (A23187) stimulation of neutrophils in calcium-free medium resulted in normal di-O-C5 (3) and CTC darkening, but a blunted chemiluminescence peak. (4) Calcium ionophore (A23187) stimulated the loss of di-O-C5 (3) and CTC fluorescence from chronic granulomatous disease neutrophils, but did not trigger an oxidative burst. Although neutrophil depolarization, calcium release from membranes, and oxidative activity are linked, these processes can clearly be separated.
Non-Targeted Metabolomics Approach Revealed Significant Changes in Metabolic Pathways in Patients with Chronic Traumatic Encephalopathy (2022)

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease that is frequently found in athletes and those who have experienced repetitive head traumas. CTE is associated with a variety of neuropathologies, which cause cognitive and behavioral impairments in CTE patients. However, currently, CTE can only be diagnosed after death via brain autopsy, and it is challenging to distinguish it from other neurodegenerative diseases with similar clinical features. To better understand this multifaceted disease and identify metabolic differences in the postmortem brain tissues of CTE patients and control subjects, we performed ultra-high performance liquid chromatography-mass spectrometry (UPLC-MS)-based non-targeted metabolomics. Through multivariate and pathway analysis, we found that the brains of CTE patients had significant changes in the metabolites involved in astrocyte activation, phenylalanine, and tyrosine metabolism. The unique metabolic characteristics of CTE identified in this study were associated with cognitive dysfunction, amyloid-beta deposition, and neuroinflammation. Altogether, this study provided new insights into the pathogenesis of CTE and suggested appealing targets for both diagnosis and treatment for the disease.
Dialyzable Form of an Extracellular Streptococcal Toxin Causing Histopathologic and Biochemical Changes in Rabbits (1972)

Earlier reports had described the presence, in supernates of streptococcal steady-state cultures, of a macromolecular toxin which causes infiltrative and necrotic lesions in the heart and liver of rabbits and changes in the serum level of certain enzymes and lipids. In the present study, following treatment of the culture supernate concentrates with trichloroacetic acid and ethanol, and dialysis, material with these biologic activities has been found, in the dialysate, and was not excluded by Sephadex G-15. The molecular weight of the toxin, by this criterion, is near that of vitamin B12.
Reversion from L1--L5 Dual to L5 Single Frequency WAAS in the Presence of RF Interference (2010)

Techniques available to sustain dual-frequency ionosphere performance when a dual-frequency airborne Global Positioning System (GPS)/wide area augmentation system (WAAS) user loses all but one GPS frequency while descending into radio frequency interference (RFI) are investigated. We are particularly interested in the case where the user transitions from L1-L5 to having L5-only since the uncertainty of the L5-only ionospheric delay estimation is larger than the case for L1-only. The goal is to provide the techniques necessary for single-frequency users to sustain a performance similar to those of dual-frequency users. The proposed techniques are 1) the code and carrier divergence technique, 2) the WAAS ionosphere threat model technique, and 3) the maximum ionospheric delay gradient model technique. The results show that all three proposed techniques provide good ionospheric delay estimation for the full duration of approach.
Adenosine A2Aagonists in development for the treatment of inflammation (2005)

Extracellular adenosine binds specifically to a family of four G protein-coupled cell-surface adenosine receptors (ARs). As the activation of the A2AAR modulates the activity of multiple inflammatory cells including neutrophils, macrophages and T lymphocytes, the receptor is considered to be a promising pharmacological target for the treatment of inflammatory disorders. Although adenosine binds nonselectively to all four AR subtypes, A2AAR selective agonists have been developed and shown to inhibit multiple manifestations of inflammatory cell activation including superoxide anion generation, cytokine production and adhesion molecule expression. A2AAR agonists are also vasodilators, but the inhibition of inflammation occurs at low doses that produce few or no cardiovascular side effects. Therefore, the selective activation of the A2AAR by these compounds holds significant potential in the treatment of inflammation.
Vibration Suppression Control Method for Trochoidal Reduction Gears under Load Conditions (2016)

This paper proposes a method for suppressing the vibrations that occur under load conditions in trochoidal reduction gears. For the proposed suppression method, a general-purpose vibration-suppression control system based on a disturbance observer is constructed without the use of a load-side sensor or the individual values of the reduction gear. The proposed method is shown to effectively improve the accuracy of the trajectory tracking. This paper proposes a new model for calculating the angular transmission error caused by a deformation of a trochoidal gear under load conditions. Using the state observer designed along with this model, the shaft torsional vibration produced under load conditions is estimated. The experimental results validate the proposed angular transmission error model and confirm the improved accuracy of the trajectory tracking.
Patient specific distortion detection and mitigation in MR images used for stereotactic radiosurgery (2022)

<i>Objective.</i>In MRI-based radiation therapy planning, mitigating patient-specific distortion with standard high bandwidth scans can result in unnecessary sacrifices of signal to noise ratio. This study investigates a technique for distortion detection and mitigation on a patient specific basis.<i>Approach.</i>Fast B0 mapping was performed using a previously developed technique for high-resolution, large dynamic range field mapping without the need for phase unwrapping algorithms. A phantom study was performed to validate the method. Distortion mitigation was validated by reducing geometric distortion with increased acquisition bandwidth and confirmed by both the B0 mapping technique and manual measurements. Images and contours from 25 brain stereotactic radiosurgery patients and 95 targets were analyzed to estimate the range of geometric distortions expected in the brain and to estimate bandwidth required to keep all treatment targets within the ±0.5 mm iso-distortion contour.<i>Main Results.</i>The phantom study showed, at 3 T, the technique can measure distortions with a mean absolute error of 0.12 mm (0.18 ppm), and a maximum error of 0.37 mm (0.6 ppm). For image acquisition at 3 T and 1.0 mm resolution, mean absolute distortion under 0.5 mm in patients required bandwidths from 109 to 200 Hz px<sup>-1</sup>for patients with the least and most distortion, respectively. Maximum absolute distortion under 0.5 mm required bandwidths from 120 to 390 Hz px<sup>-1</sup>.<i>Significance.</i>The method for B0 mapping was shown to be valid and may be applied to assess distortion clinically. Future work will adapt the readout bandwidth to prospectively mitigate distortion with the goal to improve radiosurgery treatment outcomes by reducing healthy tissue exposure.
Are women living with HIV in increased risk of complications to birth when planning elective caesarean section? A Danish nation wide population based study (2019)

Regardless of viral suppression two-thirds of women living with HIV (WLWH) in Denmark deliver by caesarean section (CS) and half of the elective CS (ECS) are performed due to mothers request. The aim of the study was to investigate if planning ECS increases risk of obstetric complications compared to planning vaginal delivery in WLWH.
Selective Inhibition of Human α-Thrombin by Cobalt(III) Schiff Base Complexes (1998)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTSelective Inhibition of Human α-Thrombin by Cobalt(III) Schiff Base ComplexesToshihiko Takeuchi, Arnd Böttcher, Cindy M. Quezada, Melvin I. Simon, Thomas J. Meade, and Harry B. GrayView Author Information Division of Biology and the Beckman Institute California Institute of Technology Pasadena, California 91125 Cite this: J. Am. Chem. Soc. 1998, 120, 33, 8555–8556Publication Date (Web):August 5, 1998Publication History Received9 April 1998Published online5 August 1998Published inissue 1 August 1998https://pubs.acs.org/doi/10.1021/ja981191xhttps://doi.org/10.1021/ja981191xrapid-communicationACS PublicationsCopyright © 1998 American Chemical SocietyRequest reuse permissionsArticle Views609Altmetric-Citations44LEARN 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-Alertsclose SUBJECTS:Cobalt,Inhibition,Inhibitors,Monomers,Peptides and proteins Get e-Alerts
Mapping the epithelial–immune cell interactome upon infection in the gut and the upper airways (2022)

Increasing evidence points towards the key role of the epithelium in the systemic and over-activated immune response to viral infection, including SARS-CoV-2 infection. Yet, how viral infection alters epithelial-immune cell interactions regulating inflammatory responses, is not well known. Available experimental approaches are insufficient to properly analyse this complex system, and computational predictions and targeted data integration are needed as an alternative approach. In this work, we propose an integrated computational biology framework that models how infection alters intracellular signalling of epithelial cells and how this change impacts the systemic immune response through modified interactions between epithelial cells and local immune cell populations. As a proof-of-concept, we focused on the role of intestinal and upper-airway epithelial infection. To characterise the modified epithelial-immune interactome, we integrated intra- and intercellular networks with single-cell RNA-seq data from SARS-CoV-2 infected human ileal and colonic organoids as well as from infected airway ciliated epithelial cells. This integrated methodology has proven useful to point out specific epithelial-immune interactions driving inflammation during disease response, and propose relevant molecular targets to guide focused experimental analysis.
Robust Wireless Power Transfer with Minimal Field Exposure Using Parity-Time Symmetric Microwave Cavities (2021)

This paper proposes cavity resonators under parity-time- ($PT$) symmetric conditions for robust wireless power transfer (WPT) with minimal exposure to electromagnetic (EM) fields. Transceiver cavities with the same resonant frequencies as that of the fundamental mode are coupled through very small evanescent waves leaking out of the lattices on the top surface of the cavities. This reduces the magnitude of the EM fields near the power-delivery system by $10$ to $10\phantom{\rule{0.1em}{0ex}}000$ times compared with conventional coil systems. Regardless of the small coupling factors between the cavities, the power-transfer efficiency is maintained at a high level due to the high quality factors of the cavities. According to coupled-mode theory, the resonant frequency of the coupled system changes sensitively with respect to the receiver position, making power delivery unstable. In this work, a feedback loop at the transmit cavity along with the saturated gain of the power amplifier achieves the $PT$-symmetric condition. The power-transfer efficiency is robust because the operating frequency is automatically locked to the resonant frequency, regardless of the operation conditions. The proposed cavity system is promising for supplementing the conventional coil system for WPT applications in which minimal field exposure is crucial. The paper is accompanied by videos demonstrating experiments.
Adaptive Control of Nonminimum Phase Processes with Application to the End Millng Process (1993)

In this work a modified model reference adaptive control design is presented for use with nonminimum phase plants which are likely to exist in end milling processes. The control law is derived and several aspects pertaining to adaptive controller design are discussed. A modified recursive least squares algorithm is used for plant parameter estimation. Simulations are shown to illustrate the effectiveness of the control algorithm. Comparison are made with existing adaptive control schemes for non-minimum phase plants.
A Hyperelastic Contact Model for the Indentation of Chondrocytes and Cartilage Extracellular Matrix (2008)

The use of micro and nanoindentation to map the elasticity of cartilage chondrocytes and extracellular matrix has been driven by the desire to understand the changes in microstructure and micromechanical properties of the tissue associated with development and with diseases such as osteoarthritis. Advances in atomic force microscopy (AFM) have facilitated application of the technique to soft tissues, allowing the concurrent imaging and mechanical probing of minute sample regions at high resolution. Examples of the capabilities of the AFM in studying cartilage biomechanics include its use in investigating changes in the elastic properties of the articular surface during development [1], comparing the dynamic elastic response at the microscale and the nanoscale [2], and measuring the elastic moduli of different zones [3].
Supplementary Figure Legends from Natural Killer Cells Are Essential for the Ability of BRAF Inhibitors to Control BRAF<sup>V600E</sup>-Mutant Metastatic Melanoma (2023)

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Chemo- and Regioselective Syntheses of Enantiopure Aminopyrrolidinones as Building Blocks for Constrained Peptidomimetics (1999)

Starting from natural asparagine the synthesis of the N-protected enantiomerically pure 3-and 4-aminopyrrolidinones (1) and (3) was accomplished.The incorporation of these building blocks into conformationally constrained peptidomimetics was demonstrated by the synthesis of the potential dopamine receptor modulator (14b) (B-PAOPA).Furthermore, Freidinger y-lactams including the protected dipeptide mimetics @a-c) and (9) were prepared.The optical integrity of the synthesis was established by NMR analysis of the ureas (10a,b).Confornationally constrained peptide analogs represent an important family of compounds employc :d for the development of enzyme inhibitors and receptor ligands.'Additionally,interesting insights into the biologically