gebhart/patrepeval huggingface dataset:
Mutations in the Parainfluenza Virus 5 Fusion Protein Reveal Domains Important for Fusion Triggering and Metastability (2013)

Paramyxovirus membrane glycoproteins F (fusion protein) and HN, H, or G (attachment protein) are critical for virus entry, which occurs through fusion of viral and cellular envelopes. The F protein folds into a homotrimeric, metastable prefusion form that can be triggered by the attachment protein to undergo a series of structural rearrangements, ultimately folding into a stable postfusion form. In paramyxovirus-infected cells, the F protein is activated in the Golgi apparatus by cleavage adjacent to a hydrophobic fusion peptide that inserts into the target membrane, eventually bringing the membranes together by F refolding. However, it is not clear how the attachment protein, known as HN in parainfluenza virus 5 (PIV5), interacts with F and triggers F to initiate fusion. To understand the roles of various F protein domains in fusion triggering and metastability, single point mutations were introduced into the PIV5 F protein. By extensive study of F protein cleavage activation, surface expression, and energetics of fusion triggering, we found a role for an immunoglobulin-like (Ig-like) domain, where multiple hydrophobic residues on the PIV5 F protein may mediate F-HN interactions. Additionally, destabilizing mutations of PIV5 F that resulted in HN trigger-independent mutant F proteins were identified in a region along the border of F trimer subunits. The positions of the potential HN-interacting region and the region important for F stability in the lower part of the PIV5 F prefusion structure provide clues to the receptor-binding initiated, HN-mediated F trigger.
Preparation, Properties, and Specific Recombination of αβ-Globin Subunits (1964)

The CM-Sephadex was prepared prior to packing by suspending it in distilled
6-Methoxy-8-amino-1,2,3,4-tetrahydroquinoline1 (1946)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXT6-Methoxy-8-amino-1,2,3,4-tetrahydroquinoline1Charles C. Price and Harry F. HerbrandsonCite this: J. Am. Chem. Soc. 1946, 68, 5, 910–911Publication Date (Print):May 1, 1946Publication History Published online1 May 2002Published inissue 1 May 1946https://pubs.acs.org/doi/10.1021/ja01209a508https://doi.org/10.1021/ja01209a508research-articleACS PublicationsRequest reuse permissionsArticle Views51Altmetric-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 Other access optionsGet e-Alertsclose Get e-Alerts
Picket fence porphyrins. Synthetic models for oxygen binding hemoproteins (1975)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPicket fence porphyrins. Synthetic models for oxygen binding hemoproteinsJames P. Collman, Robert R. Gagne, Christopher Reed, Thomas R. Halbert, George Lang, and Ward T. RobinsonCite this: J. Am. Chem. Soc. 1975, 97, 6, 1427–1439Publication Date (Print):March 1, 1975Publication History Published online1 May 2002Published inissue 1 March 1975https://pubs.acs.org/doi/10.1021/ja00839a026https://doi.org/10.1021/ja00839a026research-articleACS PublicationsRequest reuse permissionsArticle Views6317Altmetric-Citations683LEARN 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 Get e-Alerts
Neurons Containing Hypocretin (Orexin) Project to Multiple Neuronal Systems (1998)

The novel neuropeptides called hypocretins (orexins) have recently been identified as being localized exclusively in cell bodies in a subregion of the tuberal part of the hypothalamus. The structure of the hypocretins, their accumulation in vesicles of axon terminals, and their excitatory effect on cultured hypothalamic neurons suggest that the hypocretins function in intercellular communication. To characterize these peptides further and to help understand what physiological functions they may serve, we undertook an immunohistochemical study to examine the distribution of preprohypocretin-immunoreactive neurons and fibers in the rat brain. Preprohypocretin-positive neurons were found in the perifornical nucleus and in the dorsal and lateral hypothalamic areas. These cells were distinct from those that express melanin-concentrating hormone. Although they represent a restricted group of cells, their projections were widely distributed in the brain. We observed labeled fibers throughout the hypothalamus. The densest extrahypothalamic projection was found in the locus coeruleus. Fibers were also seen in the septal nuclei, the bed nucleus of the stria terminalis, the paraventricular and reuniens nuclei of the thalamus, the zona incerta, the subthalamic nucleus, the central gray, the substantia nigra, the raphe nuclei, the parabrachial area, the medullary reticular formation, and the nucleus of the solitary tract. Less prominent projections were found in cortical regions, central and anterior amygdaloid nuclei, and the olfactory bulb. These results suggest that hypocretins are likely to have a role in physiological functions in addition to food intake such as regulation of blood pressure, the neuroendocrine system, body temperature, and the sleep-waking cycle.
Uniform Resource Locators (URL) (1994)

This document specifies a Uniform Resource Locator (URL), the syntax and semantics of formalized information for location and access of resources via the Internet.
Burden of Clostridium difficile Infection in the United States (2015)

C. difficile was responsible for almost half a million infections and was associated with approximately 29,000 deaths in 2011. (Funded by the Centers for Disease Control and Prevention.).
Functional stacking of three resistance genes against Phytophthora infestans in potato (2011)

Functional stacking of broad spectrum resistance (R) genes could potentially be an effective strategy for more durable disease resistance, for example, to potato late blight caused by Phytophthora infestans (Pi). For this reason, three broad spectrum potato R genes (Rpi), Rpi-sto1 (Solanum stoloniferum), Rpi-vnt1.1 (S. venturii) and Rpi-blb3 (S. bulbocastanum) were selected, combined into a single binary vector pBINPLUS and transformed into the susceptible cultivar Desiree. Among the 550 kanamycin resistant regenerants, 28 were further investigated by gene specific PCRs. All regenerants were positive for the nptII gene and 23 of them contained the three Rpi genes, referred to as triple Rpi gene transformants. Detached leaf assay and agro-infiltration of avirulence (Avr) genes showed that the 23 triple Rpi gene transformants were resistant to the selected isolates and showed HR with the three Avr effectors indicating functional stacking of all the three Rpi genes. It is concluded that Avr genes, corresponding to the R genes to be stacked, must be available in order to assay for functionality of each stack component. No indications were found for silencing or any other negative effects affecting the function of the inserted Rpi genes. The resistance spectrum of these 23 triple Rpi gene transformants was, as expected, a sum of the spectra from the three individual Rpi genes. This is the first example of a one-step approach for the simultaneous domestication of three natural R genes against a single disease by genetic transformation.
Hepatic erythropoietin (Ep) production following double partial hepatectomy in the rat (1980)

Double partial hepatectomy (hepx) evokes an elevation in serum erythropoietin (Ep) levels in anephric hypoxic animals when compared to non-hypoxic or sham hepx controls. But this Ep response is significantly lower than that found in singly hepx, anephric hypoxic rats. Double hepx also induces numerous cytological changes in the liver. Extravascular accumulation of fat, fibrous scarring, localized necroses, and multiple abscesses, as well as decreased vascularity, occur following the second hepx. A humoral factor was detected in the serum of these animals that is capable of inducing hepatic Ep production when injected into normal rats 18 hours before nephrectomy and hypoxia. This factor, termed hepatopoietin (Hp), was previously demonstrated in the venous serum of singly hepx rats. The serum from animals subjected to double partial hepx is not as potent in inducing Ep production as the serum from singly hepx animals. The discrepancies noted between the single and double hepx groups is attributed to the necrotic cytological changes described above.
Growth and optical properties of Ag clusters deposited on poly(ethylene terephthalate) (2011)

The growth and concomitant evolution of the optical properties of Ag nano-clusters deposited on biaxially extruded poly(ethylene terephthalate) films is studied by reflectance difference spectroscopy. It is demonstrated by low energy ion scattering and simulated optical spectra that the clusters form a two-dimensional layer buried beneath the surface of the substrate. The experimental spectra are described by simulations in which different configurations of the host such as anisotropy, amorphization, and dilution are considered in an effective medium approach. The contribution of the anisotropic substrate is used to explain the resulting line shapes. We also discuss the role of the rate of change of the filling fraction with Ag coverage in the evolution of the spectra and the detection of the onset of coalescence by optical means.
β-Directing Effect of Electron-Withdrawing Groups at O-3, O-4, and O-6 Positions and α-Directing Effect by Remote Participation of 3-O-Acyl and 6-O-Acetyl Groups of Donors in Mannopyranosylations (2009)

Mannosylations of various acceptors with donors possessing an electron-withdrawing o-trifluoromethylbenzenesulfonyl, benzylsulfonyl, p-nitrobenzoyl, benzoyl, or acetyl group at O-3, O-4, or O-6 positions were found to be beta-selective except when donors had 3-O-acyl and 6-O-acetyl groups, which afforded alpha-mannosides as major products. The alpha-directing effect of 3-O-acyl and 6-O-acetyl groups was attributed to their remote participation, and the isolation of a stable bicyclic trichlorooxazine ring resulting from the intramolecular trapping of the anomeric oxocarbenium ion by 3-O-trichloroacetimidoyl group provided evidence for this remote participation. The triflate anion, counteranion of the mannosyl oxocarbenium ion, was essential for the beta-selectivity, and covalent alpha-mannosyl triflates with an electron-withdrawing group at O-3, O-4, or O-6 were detected by low-temperature NMR. The strongly electron-withdrawing sulfonyl groups, which exhibited a higher beta-directing effect in the mannosylation, made the alpha-mannosyl triflates more stable than the weakly electron-withdrawing acyl groups. We therefore proposed the mechanism for the beta-mannosylation and the origin of the beta-directing effect: the electron-withdrawing groups would stabilize the alpha-mannosyl triflate intermediate, and the subsequent reaction of the alpha-triflate (or its contact ion pair) with the acceptor would afford the beta-mannoside. The beta-selective mannosylation of a sterically demanding acceptor was achieved by employing a donor possessing two strongly electron-withdrawing benzylsulfonyl groups at O-4 and O-6 positions.
Principles of Best Practice for Community-Based Research (2003)

Community-based research (CBR) offers higher education a distinctive form of engaged scholarship and a transformative approach to teaching and learning. In this article, we propose a CBR model that is genuinely collaborative and driven by community rather than campus interests; that democratizes the creation and dissemination of knowledge; and that seeks to achieve positive social change. We demonstrate how this model translates into principles that underlie the practice of CBR in four critical areas: campus-community partnerships, research design and process, teaching and learning, and the institutionalization of centers to support CBR.
Both Estrogen Receptor Subtypes, α and β, Attenuate Cardiovascular Remodeling in Aldosterone Salt–Treated Rats (2007)

Experimental and population-based studies indicate that female gender and estrogens protect the cardiovascular system against aldosterone-induced injury. Understanding the function of estrogens in heart disease requires more precise information on the role of both estrogen receptor (ER) subtypes, ERalpha and ERbeta. Therefore, we determined whether selective activation of ERalpha or of ERbeta would confer redundant, specific, or opposing effects on cardiovascular remodeling in aldosterone salt-treated rats. The ERalpha agonist 16alpha-LE2, the ERbeta agonist 8beta-VE2, and the nonselective estrogen receptor agonist 17beta-estradiol lowered elevated blood pressure, cardiac mass, and cardiac myocyte cross-sectional areas, as well as increased perivascular collagen accumulation and vascular osteopontin expression in ovariectomized rats receiving chronic aldosterone infusion plus a high-salt diet for 8 weeks. Uterus atrophy was prevented by 16alpha-LE2 and 17beta-estradiol but not by 8beta-VE2. Cardiac proteome analyses by 2D gel electrophoresis, mass spectrometry, and peptide sequencing identified specific subsets of proteins involved in cardiac contractility, energy metabolism, cellular stress response and extracellular matrix formation that were regulated in opposite directions by aldosterone salt treatment and by different estrogen receptor agonists. We conclude that activation of either ERalpha or ERbeta protects the cardiovascular system against the detrimental effects of aldosterone salt treatment and confers redundant, as well as specific, effects on cardiac protein expression. Nonfeminizing ERbeta agonists such as 8beta-VE2 have a therapeutic potential in the treatment of hypertensive heart disease.
No-Cut Thoracoscopic Lung Plication: A New Technique for Lung Volume Reduction Surgery (1997)

Lung volume reduction surgery (LVRS) using a linear cutting stapler or laser ablation via median sternotomy or thoracoscopy is a current therapy for symptomatic emphysema. The primary causes of morbidity and mortality (as high as 20%) are existing comorbidities and prolonged air leaks secondary to visceral pleural division. We report a novel technique using minimally invasive techniques designed to achieve volume reduction while preserving the visceral pleura. A novel lung grasper and a knifeless stapler are used to permanently plicate lung tissue without cutting visceral pleura.This prospective analysis involves a consecutive series of patients who had LVRS using this method. Between May 1995 and September 1996, 32 patients underwent 50 unilateral, staged bilateral, or bilateral thoracoscopic lung plication procedures. The indications for LVRS were standard; they included severe limiting dyspnea (forced expiratory volume in one second [FEV1] = 0.68 +/- 0.05), hyperinflated lungs with flattened diaphragms on chest x-ray, and diffuse emphysema seen on chest computed tomography scan. Ventilation and perfusion scanning was used to identify potential ventilation and perfusion mismatch target areas of lung for plication.The right lung was plicated first in 25 of 32 patients (78%), and upper lobe plications predominated (77%). A mean of 9.3 +/- 0.8 staple firings were used for each unilateral plication procedure. There were no perioperative deaths. Two patients (4%) required axillary thoracotomies to repair air leaks. Mean chest tube duration was 6.3 +/- 0.5 days. Median hospital stay was 7 days (range 3-15). An Intensive Care Unit stay was required following 8 procedures (17%). Postoperative morbidity occurred in 18 (39%) of 46 procedures, including 5 cases of atrial fibrillation and 4 persistent (> 7 days) air leaks. A minimum 2 month followup was available for 22 patients (32 of 46 procedures), demonstrating a clear chest x-ray with significant improvement in ipsilateral diaphragmatic contour. Twelve patients had unilateral reduction, and 10 patients had bilateral reduction in either a staged (n = 7) or sequential at one operation (n = 3) fashion. Twenty-five (78%) of 32 procedures were associated with improved pulmonary function, with a mean increase in FEV1, in patients in this subgroup of procedures, of 43 +/- 7% for each ipsilateral plication at a mean followup of 3.8 +/- 0.5 months. For the entire group of 32 procedures, the mean improvement in measured FEV1 was 29 +/- 7%. Supplemental oxygen requirement was significantly reduced in 9 of 16 patients following plication.These data suggest that minimally invasive surgical techniques coupled with a no-cut lung plication can achieve significant lung volume reduction with favorable postoperative morbidity and mortality. Lung plication appears to hold promise as an alternative technique of LVRS.
Anti-transferrin receptor-modified amphotericin B-loaded PLA&ndash;PEG nanoparticles cure Candidal meningitis and reduce drug toxicity (2015)

Fatal fungal infections in central nervous system (CNS) can occur through hematogenous spread or direct extension. At present, hydrophobic amphotericin B (AMB) is the most effective antifungal drug in clinical trials. However, AMB is hydrophobic and therefore penetrates poorly into the CNS, and therapeutic levels of AMB are hard to achieve. The transferrin receptor (TfR/CD71) located at the blood-brain barrier mediates transferrin transcytosis. In order to enhance the receptor-mediated delivery of AMB into CNS with therapeutic level, an anti-TfR antibody (OX26)-modified AMB-loaded PLA (poly[lactic acid])-PEG (polyethylene glycol)-based micellar drug delivery system was constructed. The prepared OX26-modified AMB-loaded nanoparticles (OX26-AMB-NPs) showed significant reduction of CNS fungal burden and an increase of mouse survival time. In conclusion, OX26-AMB-NPs represent a promising novel drug delivery system for intracerebral fungal infection.
Generation of knock-in primary human T cells using Cas9 ribonucleoproteins (2015)

T-cell genome engineering holds great promise for cell-based therapies for cancer, HIV, primary immune deficiencies, and autoimmune diseases, but genetic manipulation of human T cells has been challenging. Improved tools are needed to efficiently "knock out" genes and "knock in" targeted genome modifications to modulate T-cell function and correct disease-associated mutations. CRISPR/Cas9 technology is facilitating genome engineering in many cell types, but in human T cells its efficiency has been limited and it has not yet proven useful for targeted nucleotide replacements. Here we report efficient genome engineering in human CD4(+) T cells using Cas9:single-guide RNA ribonucleoproteins (Cas9 RNPs). Cas9 RNPs allowed ablation of CXCR4, a coreceptor for HIV entry. Cas9 RNP electroporation caused up to ∼40% of cells to lose high-level cell-surface expression of CXCR4, and edited cells could be enriched by sorting based on low CXCR4 expression. Importantly, Cas9 RNPs paired with homology-directed repair template oligonucleotides generated a high frequency of targeted genome modifications in primary T cells. Targeted nucleotide replacement was achieved in CXCR4 and PD-1 (PDCD1), a regulator of T-cell exhaustion that is a validated target for tumor immunotherapy. Deep sequencing of a target site confirmed that Cas9 RNPs generated knock-in genome modifications with up to ∼20% efficiency, which accounted for up to approximately one-third of total editing events. These results establish Cas9 RNP technology for diverse experimental and therapeutic genome engineering applications in primary human T cells.
Isolation, structure and expression of cDNA and genomic clones for murine eosinophil differentiation factor (1988)

Eosinophil differentiation factor (EDF) is a recently described regulator affecting eosinophil growth and activation. cDNA clones for murine EDF were isolated by direct expression from libraries prepared from the T cell hybrid NIMP-TH1. The longest cDNA clone obtained was 1534 bp in length encoding a polypeptide of 133 amino acids. Two variant cDNAs suggesting alternative RNA processing events were detected. The EDF gene was cloned from a genomic lambda library and a region of 6727 bp encompassing the gene was sequenced. The gene contains three introns 829, 1875 and 79 bases in length and has numerous repetitive sequences. A common, possible regulatory element, including a conserved decamer, lies adjacent to the TATA boxes of the EDF and granulocyte-macrophage colony-stimulating factor (GM-CSF) genes and similar sequences are present in some other lymphokine genes. Recombinant EDF produced in monkey COS cells strongly stimulated the eosinophil lineage and also showed B-cell-growth factor II (BCGFII) activity whereas recombinant murine interleukin-3 and GM-CSF showed much broader activity towards the different myeloid lineages, were less active on eosinophils and had no BCGFII activity. The BCGFII activity of recombinant EDF together with a comparison of the BCGFII (interleukin-5) cDNA sequence with that of the EDF cDNA establishes that these two activities are the properties of a single polypeptide.
Enhancement of Single-Molecule Fluorescence Detection in Subwavelength Apertures (2005)

We report the experimental proof of molecular count rate enhancement (up to 6.5-fold) and lifetime reduction for single fluorescent molecules diffusing in subwavelength apertures milled in aluminum films. The observed enhancement dependence with the aperture diameter agrees qualitatively with numerical electromagnetic computations of the excitation power density into the aperture volume.