gebhart/patrepeval huggingface dataset:
Zinc Pyrithione Inhibits Yeast Growth through Copper Influx and Inactivation of Iron-Sulfur Proteins (2011)

Zinc pyrithione (ZPT) is an antimicrobial material with widespread use in antidandruff shampoos and antifouling paints. Despite decades of commercial use, there is little understanding of its antimicrobial mechanism of action. We used a combination of genome-wide approaches (yeast deletion mutants and microarrays) and traditional methods (gene constructs and atomic emission) to characterize the activity of ZPT against a model yeast, Saccharomyces cerevisiae. ZPT acts through an increase in cellular copper levels that leads to loss of activity of iron-sulfur cluster-containing proteins. ZPT was also found to mediate growth inhibition through an increase in copper in the scalp fungus Malassezia globosa. A model is presented in which pyrithione acts as a copper ionophore, enabling copper to enter cells and distribute across intracellular membranes. This is the first report of a metal-ligand complex that inhibits fungal growth by increasing the cellular level of a different metal.
Faculty Opinions recommendation of Global analysis of mutations driving microevolution of a heterozygous diploid fungal pathogen. (2018)

Candida albicans is a heterozygous diploid yeast that is a commensal of the human gastrointestinal tract and a prevalent opportunistic pathogen. Here, whole-genome sequencing was performed on multiple C. albicans isolates passaged both in vitro and in vivo to characterize the complete spectrum of mutations arising in laboratory culture and in the mammalian host. We establish that, independent of culture niche, microevolution is primarily driven by de novo base substitutions and frequent short-tract loss-of-heterozygosity events. An average base-substitution rate of ∼1.2 × 10-10 per base pair per generation was observed in vitro, with higher rates inferred during host infection. Large-scale chromosomal changes were relatively rare, although chromosome 7 trisomies frequently emerged during passaging in a gastrointestinal model and was associated with increased fitness for this niche. Multiple chromosomal features impacted mutational patterns, with mutation rates elevated in repetitive regions, subtelomeric regions, and in gene families encoding cell surface proteins involved in host adhesion. Strikingly, de novo mutation rates were more than 800-fold higher in regions immediately adjacent to emergent loss-of-heterozygosity tracts, indicative of recombination-induced mutagenesis. Furthermore, genomes showed biased patterns of mutations suggestive of extensive purifying selection during passaging. These results reveal how both cell-intrinsic and cell-extrinsic factors influence C. albicans microevolution, and provide a quantitative picture of genome dynamics in this heterozygous diploid species.Copyright © 2018 the Author(s). Published by PNAS. PMID: 30150418 Funding information This work was supported by: NIAID NIH HHS, United States Grant ID: R01 AI081704 NIAID NIH HHS, United States Grant ID: U19 AI110818 NIDCR NIH HHS, United States Grant ID: F31 DE023726 Wellcome Trust, United Kingdom NIAID NIH HHS, United States Grant ID: R21 AI139592 NIAID NIH HHS, United States Grant ID: R21 AI122011 NIAID NIH HHS, United States Grant ID: R21 AI112363 NIAID NIH HHS, United States Grant ID: HHSN272200900018C More Less keyboard_arrow_down
DOSMA: A deep-learning, open-source framework for musculoskeletal MRI analysis (2019)

DOSMA: A deep-learning, open-source framework for musculoskeletal MRI analysis (prerelease)
Reactions of 1-Titana- and 1-Zirconacyclopent-3-ynes with Tris(pentafluorophenyl)borane (2005)

The 1-metallacyclopent-3-ynes Cp2Ti(η4-H2C4H2) (1) (Cp = η5-cyclopentadienyl) and rac-(ebthi)Zr(η4-H2C4H2) (2) (ebthi = 1,2-ethylene-1,1'-bis(η5-tetrahydroindenyl) react with B(C6F5)3 under ring opening of the metallacycle and formation of the zwitterionic complexes [Cp2Ti]+−CH2C⋮CCH2−[B-(C6F5)3] (3) and [rac-(ebthi)Zr]+−CH2C⋮CCH2−[B-(C6F5)3] (4). Crystal structures of 3 and 4 show a but-2-yne-1,4-diyl ligand bridging the metallocenium center and the formed boranate. Complex 4 is an active catalyst for ethylene polymerization.
Physically Realizable Multi-User Radar/Communications (MURC) (2023)

Leveraging a recent method for spectrally-shaped random FM (RFM) waveform generation, in conjunction with a particular implementation of spread-spectrum signaling, a multi-user form of dual-function radar/communication (DFRC) is proposed that seeks to balance the disparate requirements of each function. Using a radar-amenable spread-spectrum multiple-access signaling scheme, receive dynamic range for sensing is preserved by exploiting high-dimensional (and thus separable) waveforms, which are specifically structured to convey encoded information in a manner that can be readily decoded at a communication receiver.
Model-free approach to the interpretation of restricted and anisotropic self-diffusion in magnetic resonance of biological tissues (2021)

Magnetic resonance imaging (MRI) is the method of choice for noninvasive studies of micrometer-scale structures in biological tissues via their effects on the time/frequency-dependent ("restricted") and anisotropic self-diffusion of water. Traditional MRI relies on pulsed magnetic field gradients to encode the signal with information about translational motion in the direction of the gradient, which convolves fundamentally different aspects-such as bulk diffusivity, restriction, anisotropy, and flow-into a single effective observable lacking specificity to distinguish between biologically plausible microstructural scenarios. To overcome this limitation, we introduce a formal analogy between measuring rotational correlation functions and interaction tensor anisotropies in nuclear magnetic resonance (NMR) spectroscopy and investigating translational motion in MRI, which we utilize to convert data acquisition and analysis strategies from NMR of rotational dynamics in macromolecules to MRI of diffusion in biological tissues, yielding model-independent quantitative metrics reporting on relevant microstructural properties with unprecedented specificity. Our model-free approach advances the state-of-the-art in microstructural MRI, thereby enabling new applications to complex multi-component tissues prevalent in both tumors and healthy brain.
Stereoselective Chloro‐Deboronation Reactions Induced by Substituted Pyridine–Iodine Chloride Complexes (2005)

Abstract A novel class of charge‐transfer complexes based on iodine chloride and substituted pyridines, which possess a number of interesting and unique structural features, can be employed to bring about a stereocontrolled chloro‐deboronation of certain vinyl boronates to generate the (1 Z )‐alkenyl chlorides in good yields. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2005)
Sunflower Protein Concentrates and Isolates’ Low in Polyphenols and Phytate (1988)

ABSTRACT Protein concentrates and isolates from sunflower ( Helianthus annuus L.), essentially free of polyphenols and/or low in phytate, were prepared from dehulled seeds by a sequential extraction procedure using organic solvents, such as hexane for defatting and acidic butanol for removing polyphenols. Phytate was removed by aqueous extraction and separation at acidic and/or alkaline conditions, depending on the relative solubility of the protein and phytate. Reduced‐phytate concentrates and isolates developed off‐colors unless the polyphenol concentration was less than 0.05%. The protein solubility profile of the reduced‐phytate products was much better than that of the defatted meal, especially below the isoelectric point.
Integration of 3D1H-magnetic resonance spectroscopy data into neuronavigation systems for tumor biopsies (2013)

Many important applications in clinical medicine can benefit from the fusion of spectroscopy data with anatomical images. For example, the correlation of metabolite profiles with specific regions of interest in anatomical tumor images can be useful in characterizing and treating heterogeneous tumors that appear structurally homogeneous. Such applications can build on the correlation of data from <i>in-vivo</i> Proton Magnetic Resonance Spectroscopy Imaging (<sup>1</sup>HMRSI) with data from genetic and <i>ex-vivo</i> Nuclear Magnetic Resonance spectroscopy. To establish that correlation, tissue samples must be neurosurgically extracted from specifically identified locations with high accuracy. Toward that end, this paper presents new neuronavigation technology that enhances current clinical capabilities in the context of neurosurgical planning and execution. The proposed methods improve upon the current state-of-the-art in neuronavigation through the use of detailed three dimensional (3D) <sup>1</sup>H-MRSI data. MRSI spectra are processed and analyzed, and specific voxels are selected based on their chemical contents. 3D neuronavigation overlays are then generated and applied to anatomical image data in the operating room. Without such technology, neurosurgeons must rely on memory and other qualitative resources alone for guidance in accessing specific MRSI-identified voxels. In contrast, MRSI-based overlays provide quantitative visual cues and location information during neurosurgery. The proposed methods enable a progressive new form of online MRSI-guided neuronavigation that we demonstrate in this study through phantom validation and clinical application.
Prevention of murine Sjogren's syndrome by local delivery of adeno-associated virus mediated Cytotoxic T-Lymphocyte Antigen 4 — immunoglobulin G fusion protein (107.1) (2011)

Abstract Dysfunction and lymphocytic infiltrations of the salivary and lachrymal glands are hallmarks of primary sjögren's syndrome (pSS), which is a chronic autoimmune epithelitis. Increasing evidence suggests that immunosuppressive agents can interrupt the progression of the disease. Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4) is a key anti-inflammatory protein for shutting down the costimulatory pathway of B7:CD28, being required in immune suppression of T regulatory cells (Treg), and subsequent immune tolerance. To better understand the modulation of CTLA4-IgG on sjögren's syndrome, we generated a recombinant type 2 adeno-associated virus vector (AAV2) to express a chimera of mouse CTLA-4 fused with a human IgG (AAV2-CTLA4IgG). The recombinant CTLA4IgG was shown to be effective at blocking B7 expression on macrophages in vitro. Expression of the CTLA4IgG in the salivary glands of C57BL/6.NOD-Aec1Aec2 mice, a model of pSS, prevented the loss of salivary gland function and decreased both T-cell and macrophage infiltrates in the glands compared with control mice. Protection of the salivary glands was also accompanied by a decrease in Th1- and Th17- cell cytokines and an increase of TGF-β1 in CTLA4IgG treated mice compared with controls. This data suggests a potential role for CTLA-4IgG in preventing sjögren's syndrome by deactivating proinflammatory T cells and promoting suppressive Treg cells.
Probing the metal-insulator transition in Ni(III)-oxide perovskites (2000)

Systematic measurements of the resistivity $\ensuremath{\rho}(T)$ and thermoelectric power $\ensuremath{\alpha}(T)$ under hydrostatic pressure have been made on single-valent perovskites of the family ${\mathrm{LnNiO}}_{3}$ $({\mathrm{L}\mathrm{n}=\mathrm{L}\mathrm{a},\mathrm{}\mathrm{P}\mathrm{r},\mathrm{}\mathrm{N}\mathrm{d},\mathrm{}\mathrm{Sm}}_{0.5}{\mathrm{Nd}}_{0.5});$ they distinguish the influences of chemical and hydrostatic pressure on the insulator-metal transition occurring at a temperature ${T}_{t}.$ The data suggest the coexistence above ${T}_{t}$ of fluctuations of more localized electrons in a Fermi-liquid background with an ordering of the two phases into a static charge-density/spin-density wave below ${T}_{t}.$
Electrochemical Depolymerization of Lignin in a Biomass‐based Solvent (2022)

Invited for this month's cover is the group of Adam Slabon at the University of Wuppertal. The image illustrates the reductive depolymerization of lignin into monomers using copper as electrocatalyst. The Research Article itself is available at 10.1002/cssc.202200718.
Rate Augmentation and Atrial Arrhythmias in DDDR Pacing (1990)

SPENCER, W.H., ET AL.: Rate Augmentation and Atrial Arrhythmias in DDDR Pacing. Dual chamber, rate‐modulated pacemakers provide the capability of augmenting the heart rate of patients with chronotropic incompetence but also may cause atrial arrhythmias because of high rate, competitive atrial pacing. We studied ten patients with two consecutive 24‐hour Holter monitors during which they were alternately programmed to either DDD or DDDR pacing in random order. Maximum heart rates (max HR) were measured at every 15‐minute interval during each 24‐hour period. DDDR pacing showed rate augmentation, 80 ± 7 average max HR when compared with DDD pacing, average max HR 76 ± 5. These results were even more striking when waking hours (7 am to 10 pm) were compared: average max HR 86 ± 7 DDDR versus 78 ± 4 average max HR DDD. Several patients showed marked rate augmentation. Seven of ten patients preferred DDDR pacing over DDD pacing. In the entire population, DDDR pacing did not result in an increased number of atrial arrhythmias (1.25 atrial events 124 hour) when compared to DDD pacing (1.75 atrial events/ 24 hour). We conclude that DDDR pacing provides heart rate augmentation during daily life in a clinical population while not resulting in a significant increase in atrial arrhythmias. (PACE, Vol. 13, December, Part 11, 1990)
European Cardiac Resynchronization Therapy Survey II: rationale and design (2014)

The Cardiac Resynchronization Therapy (CRT) Survey II is a 6 months snapshot survey initiated by two ESC Associations, the European Heart Rhythm Association and the Heart Failure Association, which is designed to describe clinical practice regarding implantation of CRT devices in a broad sample of hospitals in 47 ESC member countries. The large volume of clinical and demographic data collected should reflect current patient selection, implantation, and follow-up practice and provide information relevant for assessing healthcare resource utilization in connection with CRT. The findings of this survey should permit representative benchmarking both nationally and internationally across Europe.
Cell-to-cell spread and massive vacuole formation after Cryptococcus neoformans infection of murine macrophages (2007)

C. neoformans can escape the intracellular confines of macrophages in an actin dependent manner by cell-to-cell transfer of the yeast leading to infection of adjacent cells. In addition, complete extrusion of internalized Cn cells can lead to the formation of a massive vacuole which may be a sign of damage to the host macrophage. These observations document new outcomes for the interaction of C. neoformans with host cells that provide precedents for cell biological effects that may contribute to the pathogenesis of cryptococcal infections.
Battery Relevant Electrochemistry of Ag7Fe3(P2O7)4: Contrasting Contributions from the Redox Chemistries of Ag+ and Fe3+ (2016)

Ag7Fe3(P2O7)4 is an example of an electrochemical displacement material which contains two different electrochemically active metal cations, where one cation (Ag+) forms metallic silver nanoparticles external to the crystals of Ag7Fe3(P2O7)4 via an electrochemical reduction displacement reaction, while the other cation (Fe3+) is electrochemically reduced with the retention of iron cations within the anion structural framework concomitant with lithium insertion. These contrasting redox chemistries within one pure cathode material enable high rate capability and reversibility when Ag7Fe3(P2O7)4 is employed as cathode material in a lithium ion battery (LIB). Further, pyrophosphate materials are thermally and electrically stable, desirable attributes for cathode materials in LIBs. In this paper, a bimetallic pyrophosphate material Ag7Fe3(P2O7)4 is synthesized and confirmed to be a single phase by Rietveld refinement. Electrochemistry of Ag7Fe3(P2O7)4 is reported for the first time in the context of lithium based batteries using cyclic voltammetry and galvanostatic discharge–charge cycling. The reduction displacement reaction and the lithium (de)insertion processes are investigated using ex situ X-ray absorption spectroscopy and X-ray diffraction of electrochemically reduced and oxidized Ag7Fe3(P2O7)4. Ag7Fe3(P2O7)4 exhibits good reversibility at the iron centers indicated by ∼80% capacity retention over 100 cycles following the initial formation cycle and excellent rate capability exhibited by ∼70% capacity retention upon a 4-fold increase in current.
Lambert Sustris in Padua: fresco's en tekeningen (1993)

Abstract The Amsterdam painter Lambert Sustris stayed in Padua in the 1540s. During this period he worked, among other things, on a number of murals in palazzi and ville suburbane, and also in villas outside Padua and near Vicenza. Some of these murals still exist, others have vanished. A few drawings by Sustris associated with lost murals have however survived. In Padua, Sustris first worked in a subordinate position under Domenico Campagnola and Gualterio Padovano; later, having attained an independent status, he collaborated with the latter and with Andrea Schiavone, among others. Most of the buildings and mural decorations were designed to recreate and renew Classical Antiquity. Some were influenced by Raphael and the artistic climate in Rome and Mantua after 1530, in which followers such as Giulio Romano figured so prominently. Before going to Padua, Sustris had very likely been in Rome and perhaps in Mantua as well. His patrons in Padua, men like Alvise Cornaro and Marco Mantova Benavides, were members of the city's humanist circles, which were strongly orientated towards Rome and Classical Antiquity. The Amsterdam artist is largely responsible for the importance of the landscape in these paintings with their air of antiquity, paintings which in the case of the villas represent the earliest phase of villa decoration in the Veneto. Sustris' landscapes and figures alike clearly bear witness to a connection with Titian, whose paintings Sustris had probably furnished with landscapes earlier on. Further influences on Sustris' work during this period were primarily Raphael, Francesco Salviati and Parmigianino. Partly on the basis of the murals and drawings attributed here to Sustris, there are justifiable grounds for concluding that in recent decades the influence and position of Giuseppe Porta Salviati in Venice and Padua has been overestimated, to Sustris' disadvantage. Except for during his Padua period, the Amsterdam artist received few public commissions. He consequently sank into almost total oblivion fairly soon after his death. From as early on as the late sixteenth century some of his paintings, by virtue of their style and high quality, were taken for masterpieces by Titian.
Nucleotide Prodrugs of 2′-Deoxy-2′-spirooxetane Ribonucleosides as Novel Inhibitors of the HCV NS5B Polymerase (2013)

The limited efficacy, in particular against the genotype 1 virus, as well as the variety of side effects associated with the current therapy for hepatitis C virus (HCV) infection necessitates more efficacious drugs. We found that phosphoramidate prodrugs of 2'-deoxy-2'-spirooxetane ribonucleosides form a novel class of HCV NS5B RNA-dependent RNA polymerase inhibitors, displaying EC50 values ranging from 0.2 to >98 μM, measured in the Huh7-replicon cell line, with no apparent cytotoxicity (CC50 > 98.4 μM). Confirming recent findings, the 2'-spirooxetane moiety was identified as a novel structural motif in the field of anti-HCV nucleosides. A convenient synthesis was developed that enabled the synthesis of a broad set of nucleotide prodrugs with varying substitution patterns. Extensive formation of the triphosphate metabolite was observed in both rat and human hepatocyte cultures. In addition, after oral dosing of several phosphoramidate derivatives of compound 21 to rats, substantial hepatic levels of the active triphosphate metabolite were found.
Table S1 from IL1 Receptor Antagonist Controls Transcriptional Signature of Inflammation in Patients with Metastatic Breast Cancer (2023)

&lt;p&gt;Cytokines screening from breast tumor tissue&lt;/p&gt;
Targeting the Temporal Dynamics of Hypoxia-Induced Tumor-Secreted Factors Halts Tumor Migration (2019)

Targeting microenvironmental factors that foster migratory cell phenotypes is a promising strategy for halting tumor migration. However, lack of mechanistic understanding of the emergence of migratory phenotypes impedes pharmaceutical drug development. Using our three-dimensional microtumor model with tight control over tumor size, we recapitulated the tumor size-induced hypoxic microenvironment and emergence of migratory phenotypes in microtumors from epithelial breast cells and patient-derived primary metastatic breast cancer cells, mesothelioma cells, and lung cancer xenograft cells. The microtumor models from various patient-derived tumor cells and patient-derived xenograft cells revealed upregulation of tumor-secreted factors, including matrix metalloproteinase-9 (MMP9), fibronectin (FN), and soluble E-cadherin, consistent with clinically reported elevated levels of FN and MMP9 in patient breast tumors compared with healthy mammary glands. Secreted factors in the conditioned media of large microtumors induced a migratory phenotype in nonhypoxic, nonmigratory small microtumors. Subsequent mathematical analyses identified a two-stage microtumor progression and migration mechanism whereby hypoxia induces a migratory phenotype in the initialization stage, which then becomes self-sustained through a positive feedback loop established among the tumor-secreted factors. Computational and experimental studies showed that inhibition of tumor-secreted factors effectively halts microtumor migration despite tumor-to-tumor variation in migration kinetics, while inhibition of hypoxia is effective only within a time window and is compromised by tumor-to-tumor variation, supporting our notion that hypoxia initiates migratory phenotypes but does not sustain it. In summary, we show that targeting temporal dynamics of evolving microenvironments, especially tumor-secreted factors during tumor progression, can halt tumor migration. SIGNIFICANCE: This study uses state-of-the-art three-dimensional microtumor models and computational approaches to highlight the temporal dynamics of tumor-secreted microenvironmental factors in inducing tumor migration.
Vaccines and Broadly Neutralizing Antibodies for HIV-1 Prevention (2020)

Development of improved approaches for HIV-1 prevention will likely be required for a durable end to the global AIDS pandemic. Recent advances in preclinical studies and early phase clinical trials offer renewed promise for immunologic strategies for blocking acquisition of HIV-1 infection. Clinical trials are currently underway to evaluate the efficacy of two vaccine candidates and a broadly neutralizing antibody (bNAb) to prevent HIV-1 infection in humans. However, the vast diversity of HIV-1 is a major challenge for both active and passive immunization. Here we review current immunologic strategies for HIV-1 prevention, with a focus on current and next-generation vaccines and bNAbs.