gebhart/patrepeval huggingface dataset:
Structure-based design of submicromolar, biologically active inhibitors of trypanosomatid glyceraldehyde-3-phosphate dehydrogenase (1999)

The bloodstream stage of Trypanosoma brucei and probably the intracellular (amastigote) stage of Trypanosoma cruzi derive all of their energy from glycolysis. Inhibiting glycolytic enzymes may be a novel approach for the development of antitrypanosomatid drugs provided that sufficient parasite versus host selectivity can be obtained. Guided by the crystal structures of human, T. brucei, and Leishmania mexicana glyceraldehyde-3-phosphate dehydrogenase, we designed adenosine analogs as tight binding inhibitors that occupy the pocket on the enzyme that accommodates the adenosyl moiety of the NAD+ cosubstrate. Although adenosine is a very poor inhibitor, IC50 approximately 50 mM, addition of substituents to the 2' position of ribose and the N6-position of adenosine led to disubstituted nucleosides with micromolar to submicromolar potency in glyceraldehyde-3-phosphate dehydrogenase assays, an improvement of 5 orders of magnitude over the lead. The designed compounds do not inhibit the human glycolytic enzyme when tested up to their solubility limit (approximately 40 microM). When tested against cultured bloodstream T. brucei and intracellular T. cruzi, N6-(1-naphthalenemethyl)-2'-(3-chlorobenzamido)adenosine inhibited growth in the low micromolar range. Within minutes after adding this compound to bloodstream T. brucei, production of glucose-derived pyruvate ceased, parasite motility was lost, and a mixture of grossly deformed and lysed parasites was observed. These studies underscore the feasibility of using structure-based drug design to transform a mediocre lead compound into a potent enzyme inhibitor. They also suggest that energy production can be blocked in trypanosomatids with a tight binding competitive inhibitor of an enzyme in the glycolytic pathway.
Enhanced stimulated raman scattering of solvent due to anharmonic energy transfer from resonance raman solute molecules (2020)

A new nonlinear optical process, named enhanced stimulated Raman scattering (ESRS), is reported for the first time from resonance Raman in β-carotene-methanol solution. It is well known that absorption decreases the efficiency of the nonlinear optical and laser processes; however, we observed enhanced stimulated Raman peaks at the first and second Stokes from methanol solvent at 2834 cm<sup>-1</sup> with the addition of β-carotene solutes. This enhanced SRS effect in methanol is attributed to the resonance Raman (RR) process in β-carotene, which creates a significant number of vibrations from RR and the excess vibrations are transferred to methanol from anharmonic vibrational interactions between the β-carotene solutes and the methanol solvent, and consequently leads to the increased Raman gain.
Head Imaging Using Head Transmit Coil And Body Transmit Coil at 3T (2003)

S/m. The body coil is a 16-element band-pass birdcage with mean diameter of 0.6m and length of 0.4m. The head coil is a 12-element band-pass half-closed birdcage with diameter of 0.3m and length of 0.23m. The head coil is located at the center of the body coil. They share the same RF shield with diameter of 0.68m and length of 1m. All of the capacitors in coil rungs and rings are modeled by assigning capacitive loads in the gaps opened at their locations in the body coil and head coil. The capacitor values are then adjusted such that they resonate at f = 128MHz with one decoupled from the other. The pin diode decoupling is modeled by adding large value resistors (~15k ) in each rung of the non-transmit coil. Two sinusoidal voltage sources with the same amplitude but 90° phase difference are used to drive either the head coil or the body coil in quadrature. When the head coil is used as the transmit coil, the body coil is decoupled, and vice versa. A human body model, which has 23 distinct tissue types with conductivities and permittivities set to their values at the frequency of 128MHz (Remcom, Inc., State College, PA), is then simulated in the head coil and body coil such that the head is centered inside the head coil (see Fig 1). Steady-state solutions are recorded and B1-field in the laboratory frame is converted to B1 + -field in the rotating frame using the formula in Ref [1]. The magnitude of B1 + -field is then rescaled to provide the B1 + -field average over the central transverse slice of the human head model equal to 20µT for both body coil transmit and head coil transmit cases. Results In Fig. 2, we show the magnitude of B1 + -field distribution inside the head for three orthogonal planes for the cases of head coil transmit (top) and body coil transmit (bottom). The FoV along the z-axis is 21cm. The higher B1 + -field in the center of the head is clearly due to the dielectric effects of the head tissues [2,3]. For body coil transmitting, the overall B1 + -field uniformity in sagittal and coronal planes is better than B1 + -field for head coil transmitting. In the transverse plane, the B1 + -field uniformity is comparable for the two cases. However, SAR calculation reveals that, for body coil transmitting, it is the local SAR per 10-gram mass that reaches the IEC’s local SAR limit sooner than the head SAR. It gives the maximum RF duty cycle of 2.3% in order to follow the IEC’s local SAR guideline (≤10W/kg) [4]. For head coil transmitting, calculation shows that head SAR and local SAR reach the IEC’s SAR limits at essentially the same duty cycle. Partial body and whole body SAR values are not shown because they do not appear to be the limiting factors in both cases. The head coil transmit case allows 3.2% duty cycle as compared to 2.3% duty cycle for the body coil transmit case for the same B1
Effect of fiber structure on dialysate flow profile and hollow-fiber hemodialyzer reliability: CT perfusion study (2008)

The undulated-fiber type was found to have more uniform, consistent dialysate flow profiles. It is believed that this type of hemodialyzer will be found helpful for measurement and prescription of the delivered hemodialysis dose due to its better consistency.
Cycling activity of benign prostatic epithelial cells during long‐term androgen blockade: evidence for self‐renewal of luminal cells (1998)

Combined androgen blockade (CAB) therapy (LHRH agonist and flutamide) for 6 months leads to marked regressive changes of the prostate gland. This is associated with a reduction in the ratio of luminal to basal cells in the peripheral zone (PZ) in hyperplastic glands of the transitional zone (TZ). To examine the cycling activity of luminal and basal cells, double immunostaining was performed. For precise definition of basal cells, the basal cell-specific antibody 34βE12 was used, while cycling cells were identified by the MIB-1 antibody. In 6-month-treated specimens, the fraction of cycling luminal cells increased from 03 to 25 per cent in the PZ and from 02 to 39 per cent in the TZ. This was associated with an inversion of the ratio of MIB-1-labelled luminal to basal cells, with values of 57:1 (PZ) and 39:1 (TZ), compared with 1:4 (PZ) and 1:5 (TZ) in untreated specimens. The predominance continued for at least 11 years of CAB. The findings strongly suggest that luminal cells are capable of self-renewal under conditions of low androgen levels. The substantial decrease of prostatic volume on long-term CAB implies that cell loss outweighs cell proliferation. Copyright © 1998 John Wiley & Sons, Ltd.
Angiotensin II‐induced microvascular responses in mouse brain (2009)

Although angiotensin II (AngII)‐induced hypertension increases the risk for ischemic stroke, the mechanisms linking AngII to this cardiovascular disease remain poorly understood. We determined whether AngII (delivered over a 2 wk period with an Alzet pump) promotes leukocyte (LECA)‐ and platelet (PECA)‐endothelial cell adhesion in cerebral venules and/or alters blood brain barrier (BBB) permeability in C57Bl/6 (WT), AT1‐R −/− mice, and AT1‐R −/− ‐&gt;WT bone marrow chimeras (BMC). Intravital video microscopy was used to monitor blood cell adhesion from a cranial window. AngII infusion induced dose‐dependent (400‐2000 ng/kg/min) increases in mean arterial pressure (MAP), LECA, and PECA. AT1‐R −/− , AT1‐R −/− ‐&gt;WT BMC, and WT mice treated with Losartan (25 mg/kg/day) all exhibited no changes in MAP, LECA and PECA in response to AngII. BBB permeability, measured by Evans blue extravasation, was increased in response to AngII in WT and AT1‐R −/− ‐&gt;WT BMC mice, but not in AT1‐R −/− mice and WT mice treated with Losartan. These findings implicate AT1‐receptors (AT1‐R) on blood cells in the inflammatory and pro‐thrombogenic phenotype induced during AngII‐induced hypertension. The accompanying BBB dysfunction appears to involve AT1‐R on endothelial cells, rather than blood cells. (Supported by HL26441)
Lab to Market: Where the Rubber Meets the Road for Sustainable Chemical Technologies (2021)

ADVERTISEMENT RETURN TO ISSUEEditorialNEXTLab to Market: Where the Rubber Meets the Road for Sustainable Chemical TechnologiesBala SubramaniamBala SubramaniamMore by Bala Subramaniamhttp://orcid.org/0000-0001-5361-1954, David AllenDavid AllenMore by David Allenhttp://orcid.org/0000-0001-6646-8755, King Kuok (Mimi) HiiKing Kuok (Mimi) HiiMore by King Kuok (Mimi) Hiihttp://orcid.org/0000-0002-1163-0505, Juan ColbergJuan ColbergMore by Juan Colberg, and Thalappil PradeepThalappil PradeepMore by Thalappil Pradeephttp://orcid.org/0000-0003-3174-534XCite this: ACS Sustainable Chem. Eng. 2021, 9, 8, 2987–2989Publication Date (Web):March 1, 2021Publication History Received10 February 2021Published online1 March 2021Published inissue 1 March 2021https://pubs.acs.org/doi/10.1021/acssuschemeng.1c00980https://doi.org/10.1021/acssuschemeng.1c00980editorialACS PublicationsCopyright © Published 2021 by American Chemical Society. This publication is available under these Terms of Use. Request reuse permissions This publication is free to access through this site. Learn MoreArticle Views1152Altmetric-Citations2LEARN 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 PDF (1 MB) Get e-AlertscloseSUBJECTS:Biomass,Energy,Green chemistry,Industrial manufacturing,Sustainability Get e-Alerts
BOSS: Beta-mixture Unsupervised Oligodendrocytes Segmentation System (2022)

ABSTRACT To develop reparative therapies for multiple sclerosis (MS), we need to better understand the physiology of loss and replacement of oligodendrocytes, the cells that make myelin and the target of damage in MS. In vivo two-photon fluorescence microscopy allows direct visualization of oligodendrocytes in transgenic mouse models, and promises a deeper understanding of the longitudinal dynamics of replacing oligodendrocytes after damage. However, the task of tracking oligodendrocytes requires extensive human effort and is especially challenging in three-dimensional images. While several models exist for automatically annotating cells in two-dimensional images, few models exist to annotate cells in three-dimensional images and even fewer are designed for tracking cells in longitudinal imaging. Furthermore, the complexity of processes and myelin formed by individual oligodendrocytes can result in the failure of algorithms that are specifically designed for tracking cell bodies alone. Here, we propose a novel beta-mixture unsupervised oligodendrocyte segmentation system (BOSS) that can segment and track oligodendrocytes in three-dimensional images over time that requires minimal human input. We evaluated the performance of the BOSS model on a set of eight images obtained longitudinally. We showed that the BOSS model can segment and track oligodendrocytes similarly to a blinded human observer. Our method offers many advantages, as it does not require fully curated data, reduces computational time, and most importantly recapitulates cell dynamic patterns observed by manually tracking oligodendrocytes. Although BOSS was developed to apply to our studies on oligodendrocytes, we anticipate that it can be modified to study four-dimensional in vivo data of any brain cell.
Isolation of a chondroitin sulfate proteoglycan from a rat yolk sac tumor and immunochemical demonstration of its cell surface localization. (1981)

A proteoglycan was isolated from ascites fluid produced by a rat yolk sac tumor. The glycosaminoglycan chains of the proteoglycan are all sensitive to digestion with chondroitinase ABC and about 90% are sensitive to chondroitinase AC. The proteoglycan contains 5% protein. Amino acid analysis revealed a high content of serine and glycine which together constitute 37% of the amino acids. Glutamic acid (glutamine) and aspartic acid (asparagine) are also abundant. Galactosamine accounts for 97% of the hexosamine and the remainder is glucosamine. These characteristics indicate that the glycosaminoglycan side chains of this proteoglycan are predominantly chondroitin sulfate with a smaller amount of dermatan sulfate. Antibodies to the proteoglycan were prepared by immunization of a rabbit with purified alkali-treated proteoglycan. Affinity-purified antibodies from the antiserum immunoprecipitated (35S)sulfate-labeled radioactivity from culture media of the yolk sac tumor cells known to contain chondroitin sulfate proteoglycan. This binding was inhibited by the intact purified proteoglycan but not by proteoglycan treated with papain, suggesting dependence of the reactivity of the antibodies on integrity of the protein part of the proteoglycan. Immunofluorescence of the cultured yolk sac tumor cells revealed localization of immune reactive proteoglycans at the cell surface.
Real-time monitoring of immediate drug response and adaptation upon repeated treatment in a microfluidic chip system (2022)

Microfluidic tissue culture and organ-on-a-chip models provide efficient tools for drug testing in vivo and are considered to become the basis of in vitro test systems to analyze drug response, drug interactions and toxicity to complement and reduce animal testing. A major limitation is the efficient recording of drug action. Here we present an efficient experimental setup that allows long-term cultivation of cells in a microfluidic system in combination with continuous recording of luciferase reporter gene expression. The system combines a sensitive cooled luminescence camera system in combination with a custom build miniaturized incubation chamber. The setup allows to monitor time-dependent activation, but also the end of drug response. Repeated activation and recovery as well as varying durations of drug treatment periods can be monitored, and different modes of drug activity can be visualized.
Experiments and simulations on short chain fatty acid production in a colonic bacterial community (2018)

Understanding how production of specific metabolites by gut microbes is modulated by interactions with surrounding species and by environmental nutrient availability is an important open challenge in microbiome research. As part of this endeavor, we explore interactions between F. prausnitzii, a major butyrate producer, and B. thetaiotaomicron, an acetate producer, under three different in vitro media conditions in monoculture and coculture. In silico Genome-scale dynamic flux balance analysis (dFBA) models of metabolism in the system using COMETS (Computation of Microbial Ecosystems in Time and Space) are also tested for explanatory, predictive and inferential power. Experimental findings indicate enhancement of butyrate production in coculture relative to F. prausnitzii monoculture but defy a simple model of monotonic increases in butyrate production as a function of acetate availability in the medium. Simulations recapitulate biomass production curves for monocultures and accurately predict the growth curve of coculture total biomass, using parameters learned from monocultures, suggesting that the model captures some aspects of how the two bacteria interact. However, a comparison of data and simulations for environmental acetate and butyrate changes suggest that the organisms adopt one of many possible metabolic strategies equivalent in terms of growth efficiency. Furthermore, the model seems not to capture subsequent shifts in metabolic activities observed experimentally under low-nutrient regimes. Some discrepancies can be explained by the multiplicity of possible fermentative states for F. prausnitzii. In general, these results provide valuable guidelines for design of future experiments aimed at better determining the mechanisms leading to enhanced butyrate in this ecosystem.
Refractive errors and incident cataracts: the Beaver Dam Eye Study. (2001)

These data support the cross-sectional association between myopia and nuclear cataract seen in other population-based studies, but provide no evidence of a relationship between myopia and 5-year incident cataract. Hyperopia may be related weakly to incident nuclear and cortical cataract.
Novel Method for the Synthesis of Molecularly Imprinted Polymer Bead Libraries (2004)

Abstract Summary: A novel method for the synthesis of spherical molecularly imprinted polymer (MIP) beads by suspension polymerization in mineral oil is described. The usefulness of the method was demonstrated by the synthesis of a propranolol imprinted MIP library. The composition of the library was generated by statistical experimental design. Multivariate data analysis correlated the screening data, obtained by a radioligand binding assay, to the composition of the MIPs. Light micrograph of MIP beads (MIP 4; size fraction 25–50 μm). magnified image Light micrograph of MIP beads (MIP 4; size fraction 25–50 μm).
Probability table compression for handwritten character recognition (2004)

This paper presents a new probability table memory compression method based on mixture models and its application to N-tuple recognizers and N-gram character language models. Joint probability tables are decomposed into lower dimensional probability components and their mixtures. The maximum likelihood parameters of the mixture models are trained by the expectation maximization (EM) algorithm and quantized to one byte integers. Probability elements that mixture models do not estimate reliably are kept separately. Experimental results with on-line handwritten UNIPEN uppercase and lowercase characters show that the total memory size of an on-line scanning N-tuple recognizer is reduced from 12.3 MB to 0.66 MB bytes, while the recognition rate drops from 91.64% to 91.13% for uppercase characters and from 88.44% to 87.31% for lowercase characters. The N-gram character language model was compressed from 73.6 MB to 0.58 MB with minimal reduction in performance.
Protein-Structure Assisted Optimization of 4,5-Dihydroxypyrimidine-6-Carboxamide Inhibitors of Influenza Virus Endonuclease (2017)

Abstract Influenza is a serious hazard to human health that causes hundreds of thousands of deaths annually. Though vaccines and current therapeutics can blunt some of the perilous impact of this viral infection, new treatments are needed due to the constantly evolving nature of this virus. Recently, our growing understanding of an essential influenza viral protein, PA, has led to the development of focused libraries of new small molecules that specifically target the active site of the PA influenza endonuclease, which we report here. Our overarching approach has been to proactively develop lead inhibitors that are less likely to rapidly develop clinical resistance by optimizing inhibitors that retain activity against induced resistant mutants. Here, we report details behind the discovery of new potent inhibitors of wild type and resistant mutant endonucleases along with their high-resolution co-crystal structure-activity relationships. These results add to our understanding of nuclease protein targets and potentially serve as starting points for a new therapeutic approach to the treatment of influenza.
Prognosis of early pre-discharge and late left ventricular dilatation by cardiac magnetic resonance imaging after acute myocardial infarction (2021)

To study the long-term prognosis of early pre-discharge and late left ventricular (LV) dilatation in patients with first ST-elevation myocardial infarction (STEMI) treated by percutaneous coronary intervention (PCI) and contemporary medical therapy. Long-term follow-up > 15 years was available in 53 consecutive patients (55 ± 13 years) with first STEMI. Late gadolinium enhanced (LGE) cardiac magnetic resonance imaging (CMR) was obtained at baseline 5 ± 3 days and follow-up 8 ± 3 months after STEMI to measure LV function, volumes and infarct size. Early pre-discharge dilatation was defined as increased left ventricular end-diastolic volume index (LVEDVi) at baseline CMR with > 97 ml/m<sup>2</sup> for males and > 90 ml/m<sup>2</sup> for females. Late dilatation was defined as initially normal LVEDVi, which increased ≥ 20% at follow-up. Early dilatation was present in 7 patients (13%), whereas late dilatation occurred in 11 patients (21%). Patients with early LV dilatation had highest mortality (57%), whereas patients with late dilatation had similar mortality (27%) compared to patients without dilatation (26%). Multivariate Cox analysis showed that age (P < 0.001), ejection fraction at baseline (P < 0.01) and early dilatation (P < 0.01) were independent predictors of death. Early dilatation qualified as an exclusive independent predictor of long-term mortality after adjustment for age and ejection fraction (P < 0.05, hazard ratio: 2.2, 95% confidence interval: 1.2 to 7.9). Early pre-discharge LV dilatation by CMR enabled strong long-term risk stratification after STEMI. The high mortality of early LV dilatation underscores the clinical importance of this post-infarction complication, which occurred despite PCI and contemporary medical therapy.
Nanoscale Probing of Image-Potential States and Electron Transfer Doping in Borophene Polymorphs (2021)

Because synthetic 2D materials are generally stabilized by interfacial coupling to growth substrates, direct probing of interfacial phenomena is critical for understanding their nanoscale structure and properties. Using field-emission resonance spectroscopy with an ultrahigh vacuum scanning tunneling microscope, we reveal Stark-shifted image-potential states of the <i>v</i><sub>1/6</sub> and <i>v</i><sub>1/5</sub> borophene polymorphs on Ag(111) with long lifetimes, suggesting high borophene lattice and interface quality. These image-potential states allow the local work function and interfacial charge transfer of borophene to be probed at the nanoscale and test the widely employed self-doping model of borophene. Supported by apparent barrier height measurements and density functional theory calculations, electron transfer doping occurs for both borophene phases from the Ag(111) substrate. In contradiction with the self-doping model, a higher electron transfer doping level occurs for denser <i>v</i><sub>1/6</sub> borophene compared to <i>v</i><sub>1/5</sub> borophene, thus revealing the importance of substrate effects on borophene electron transfer.