gebhart/patrepeval huggingface dataset:
Novel approach for accurate tissue-based protein colocalization and proximity microscopy (2017)

Fluorescence colocalization microscopy is frequently used to assess potential links between distinct molecules; however, this method can lead to striking false-positive results and erroneous conclusions. Here we developed a novel approach with more sophisticated mathematical colocalization analyses together with visualization of physical proximity using fluorescence resonance energy transfer (FRET). To verify our results we used the proximity ligation assay (PLA). With these methods we could demonstrate that distinct neurodegeneration-related proteins either not or only rarely interact in human brain tissue.
Strategies for New Antimicrobial Proteins and Peptides: Lysozyme and Aprotinin as Model Molecules (2002)

The increasing development of bacterial resistance to traditional antibiotics has reached alarming levels, thus necessitating the strong need to develop new antimicrobial agents. These new antimicrobials should possess both novel modes of action as well as different cellular targets compared with the existing antibiotics. Lysozyme, muramidase, and aprotinin, a protease inhibitor, both exhibit antimicrobial activities against different microorganisms, were chosen as model proteins to develop more potent bactericidal agents with broader antimicrobial specificity. The antibacterial specificity of lysozyme is basically directed against certain Gram-positive bacteria and to a lesser extent against Gram-negative ones, thus its potential use as antimicrobial agent in food and drug systems is hampered. Several strategies were attempted to convert lysozyme to be active in killing Gram-negative bacteria which would be an important contribution for modern biotechnology and medicine. Three strategies were adopted in which membrane-binding hydrophobic domains were introduced to the catalytic function of lysozyme, to enable it to damage the bacterial membrane functions. These successful strategies were based on either equipping the enzyme with a hydrophobic carrier to enable it to penetrate and disrupt the bacterial membrane, or coupling lysozyme with a safe phenolic aldehyde having lethal activity toward bacterial membrane. In a different approach, proteolytically tailored lysozyme and aprotinin have been designed on the basis of modifying the derived peptides to confer the most favorable bactericidal potency and cellular specificity. The results obtained from these strategies show that proteins can be tailored and modelled to achieve particular functions. These approaches introduced, for the first time, a new conceptual utilization of lysozyme and aprotinin, and thus heralded a great opportunity for potential use in drug systems as new antimicrobial agent.
Wide‐Range Achievement Test (2010)

Abstract The Wide‐Range Achievement Test (WRAT) was developed in the 1930s by psychologist Joseph Jastak and first published for operational use in 1946. Two subsequent revisions of the WRAT were issued in 1984 (WRAT‐R) and 1993 (WRAT 3; Wilkinson, 1993). The current edition—WRAT 4—retains the focus of the previous editions by providing norm‐referenced measures of reading, spelling, and mathematics computation. Designed for use with individuals age 5–94 years, the WRAT 4 contains four subtests: word reading, sentence comprehension, spelling, and mathematics computation. The reading and sentence comprehension tests must be administered individually, whereas the spelling and mathematics computation tests may be administered either individually or in small groups. The administration time required is 15–45 minutes, depending on the age of the test taker. The various editions of the WRAT have enjoyed widespread use due to their ease of administration and scoring and the amount of information obtained in a relatively brief amount of testing time.
Nuclear magnetic resonance spectroscopy of lanthanide complexes with a tetraacetic tetraaza macrocycle. Unusual conformation properties (1980)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTNuclear magnetic resonance spectroscopy of lanthanide complexes with a tetraacetic tetraaza macrocycle. Unusual conformation propertiesJ. F. DesreuxCite this: Inorg. Chem. 1980, 19, 5, 1319–1324Publication Date (Print):May 1, 1980Publication History Published online1 May 2002Published inissue 1 May 1980https://pubs.acs.org/doi/10.1021/ic50207a042https://doi.org/10.1021/ic50207a042research-articleACS PublicationsRequest reuse permissionsArticle Views2498Altmetric-Citations298LEARN 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
Heparin inhibits the flow adhesion of sickle red blood cells to P-selectin (2002)

The adhesion of sickle erythrocytes to vascular endothelium is important to the generation of vascular occlusion. Interactions between sickle cells and the endothelium use several cell adhesion molecules. We have reported that sickle cell adhesion to endothelial cells under static conditions involves P-selectin. Others have shown that sickle cell adhesion is decreased by unfractionated heparin, but the molecular target of this inhibition has not been defined. We postulated that the adhesion of sickle cells to P-selectin might be the pathway blocked by unfractionated heparin. In this report we demonstrate that the flow adherence of sickle cells to thrombin-treated human vascular endothelial cells also uses P-selectin and that this component of adhesion is inhibited by unfractionated heparin. We also demonstrate that sickle cells adhere to immobilized recombinant P-selectin under flow conditions. This adhesion too was inhibited by unfractionated heparin, in a concentration range that is clinically attainable. These findings and the general role of P-selectin in initiating adhesion of blood cells to the endothelium suggest that unfractionated heparin may be useful in preventing painful vascular occlusion. A clinical trial to test this hypothesis is indicated.
Model for1/fFlux Noise in SQUIDs and Qubits (2007)

We propose a model for 1/f flux noise in superconducting devices (f is frequency). The noise is generated by the magnetic moments of electrons in defect states which they occupy for a wide distribution of times before escaping. A trapped electron occupies one of the two Kramers-degenerate ground states, between which the transition rate is negligible at low temperature. As a result, the magnetic moment orientation is locked. Simulations of the noise produced by randomly oriented defects with a density of 5x10(17) m(-2) yield 1/f noise magnitudes in good agreement with experiments.
Synthetic fragments of calmodulin calcium-binding site III. A test of the acid pair hypothesis. (1990)

The acid pair hypothesis describing the interaction of calcium with the helix-loop-helix conformation of EF hands in calmodulin and related proteins predicts that these calcium-binding sites will have increased affinity for calcium if the anionic amino acid dentates in the loop region which interact directly with the cation are paired on the axial vertices of the resulting octahedral arrangement of chelating residues about the cation. As a test of this hypothesis, synthetic 33 residue analogs of bovine brain calmodulin calcium-binding site III have been prepared by the solid-phase method and analyzed for calcium affinity. The native sequence has a Kd of 735 microM for calcium and contains three anionic ligands which assume the +x, +y, and -z coordinates of the octahedral arrangement about the cation, thus precluding any pairing of the anionic ligands. This dissociation constant is 26 times weaker than that obtained from a synthetic analog of the sequentially homologous calcium-binding site III of rabbit skeletal TnC (Kd = 28 microM) which has four anionic ligands paired on the x and z axes. An analog of calmodulin site III with substitutions in the chelating residues at positions 1, 3, 5, 7, 9, and 12 of the 12-residue loop region to make these positions identical to those of rabbit skeletal troponin C site III decreased the calcium dissociation constant of the calmodulin peptide to 19 microM, similar to the troponin C peptide. Two synthetic analogs of calmodulin site III which contain three anionic ligands with two ligands paired on the x axis and two on the z axis have a Kd for calcium of 524 and 59 microM, respectively. This study provides strong support for and a better definition of the acid pair hypothesis and further demonstrates the usefulness of synthetic calcium-binding fragments in delineating the mechanism of calcium regulation of calmodulin and related proteins.
Quantitative Assessment of Citric Acid in Lemon Juice, Lime Juice, and Commercially-Available Fruit Juice Products (2008)

Lemon and lime juice, both from the fresh fruit and from juice concentrates, provide more citric acid per liter than ready-to-consume grapefruit juice, ready-to-consume orange juice, and orange juice squeezed from the fruit. Ready-to-consume lemonade formulations and those requiring mixing with water contain < or =6 times the citric acid, on an ounce-for-ounce basis, of lemon and lime juice.
Quantitation of 6-thioguanine in peripheral blood leukocyte DNA in Crohn's disease patients on maintenance 6-mercaptopurine therapy (1996)

The effects of 6-mercaptopurine (6MP) in inflammatory bowel disease are believed to be primarily mediated by its metabolite 6-thioguanine (6TG). Our aim was to develop an assay for measuring leukocyte DNA 6TG levels in patients with Crohn's disease, and to correlate them with levels of 6TG in erythrocytes. Heparinized blood was obtained from 15 adolescent Crohn's disease patients receiving 6MP at an average dose of 1.3 mg.kg-1 day-1 (range 0.8-1.6 mg.kg-1 day-1) for a mean of 23.7 months (range 3-71 months). Leukocyte DNA and erythrocyte 6TG levels were measured by an HPLC assay. Leukocyte 6TG levels ranged from 100 to 2305 pmol/mg DNA, while erythrocyte 6TG levels ranged from 64 to 1038 pmol/8 x 10(8) red blood cells, demonstrating significant interpatient variability. Leukocyte DNA 6TG levels correlated directly with erythrocyte 6TG levels, as measured by the Spearman rank correlation coefficient (p < 0.05). The HPLC measurement of erythrocyte and leukocyte DNA 6TG levels can be useful clinically in monitoring compliance, as well as perhaps to tailor drug metabolite levels to achieve the desired clinical effect.
Tench Coxe and the Early Republic (1979)

Tench Coxe participated in or commented on most of the major events in American history from the Revolution to the 1820s. His long career of public involvement embodies many of the significant historical themes of the time: he was a Philadelphia aristocrat, a loyalist out of opportunism, a merchant during the period of economic adjustment in the 1780s, a grandiose land speculator, a Federalist with Alexander Hamilton and later a Republican with Thomas Jefferson, a nationalist theorist, a major prophet of industrial growth, and a prolific journalist. As this biography conclusively demonstrates, Coxe's role was considerably more consequential in the early history of the nation than has hitherto been supposed.Coxe's career is more interesting because it is paradoxical. Although he persistently aspired to fame as a public official, the posthumous recognition he has received is the result of his extensive writings on economic and mercantile policy. This volume expecially emphasizes Coxe's farsighted views and achievements as a political economist: his support of protective tarrifts, his advocacy of laborsaving machinery, and his prescient belief that cotton growing was the key to American economic independence and industrialization.Based on more than a decade's work in the voluminous collection of Coxe Papers, to which Jacob Cooke was given exclusive access, this biography provides much information on the operations of the Treasury Department under Alexander Hamilton, whom Coxe served as assistant secretary, and on the development of political parties. A Federalist apostate, Coxe was representative of a small but historically significant wing of his party that enthusiastically endorsed the fiscal policies of Hamilton while championing the commercial policies of Jefferson. Coxe openly became one of the Virginian's most active supporters, as a state party leader, national campaign coordinator, and partisan polemicist.Originally published in 1978.A UNC Press Enduring Edition -- UNC Press Enduring Editions use the latest in digital technology to make available again books from our distinguished backlist that were previously out of print. These editions are published unaltered from the original, and are presented in affordable paperback formats, bringing readers both historical and cultural value.Yet in the course of his career Coxe managed to alienate Jefferson and most of his other powerful associates, including Hamilton and John Adams. These men and others have left damaging portraits of Coxe. Professor Cooke examines the paradox presented by such uncomplimentary assessments of a man of uncommon ability and conspicuous accomplishments and at the same time opens for readers many new views of the stage upon which Tench Coxe played out his frustrated ambitions -- the whole political and economic life of the early Republic.
Small-molecule ligands bind to a distinct pocket in Ras and inhibit SOS-mediated nucleotide exchange activity (2012)

The Ras gene is frequently mutated in cancer, and mutant Ras drives tumorigenesis. Although Ras is a central oncogene, small molecules that bind to Ras in a well-defined manner and exert inhibitory effects have not been uncovered to date. Through an NMR-based fragment screen, we identified a group of small molecules that all bind to a common site on Ras. High-resolution cocrystal structures delineated a unique ligand-binding pocket on the Ras protein that is adjacent to the switch I/II regions and can be expanded upon compound binding. Structure analysis predicts that compound-binding interferes with the Ras/SOS interactions. Indeed, selected compounds inhibit SOS-mediated nucleotide exchange and prevent Ras activation by blocking the formation of intermediates of the exchange reaction. The discovery of a small-molecule binding pocket on Ras with functional significance provides a new direction in the search of therapeutically effective inhibitors of the Ras oncoprotein.
Perioperative Hypothermia: Use and Therapeutic Implications (2009)

Perioperative cerebral ischemic insults are common in some surgical procedures. The notion that induced hypothermia can be employed to improve outcome in surgical patients has persisted for six decades. Its principal application has been in the context of cardiothoracic and neurosurgery. Mild (32-35 degrees C) and moderate (26-31 degrees C) hypothermia have been utilized for numerous procedures involving the heart, but intensive research has found little or no benefit to outcome. This may, in part, be attributable to confounding effects associated with rewarming and lack of understanding of the mechanisms of injury. Evidence of efficacy of mild hypothermia is absent for cerebral aneurysm clipping and carotid endarterectomy. Deep hypothermia (18-25 degrees C) during circulatory arrest has been practiced in the repair of congenital heart disease, adult thoracic aortas, and giant intracranial aneurysms. There is little doubt of the protective efficacy of deep hypothermia, but continued efforts to refine its application may serve to enhance its utility. Recent evidence that mild hypothermia is efficacious in out-of-hospital cardiac arrest has implications for patients incurring anoxic or global ischemic brain insults during anesthesia and surgery, or perioperatively. Advances in preclinical models of ischemic/anoxic injury and cardiopulmonary bypass that allow definition of optimal cooling strategies and study of cellular and subcellular events during perioperative ischemia can add to our understanding of mechanisms of hypothermia efficacy and provide a rationale basis for its implementation in humans.
Immunohistochemical Expression of WT1 by Desmoplastic Small Round Cell Tumor (2000)

Desmoplastic small round cell tumors (DSRCTs) present a reciprocal chromosomal translocation, t(11;22)(p13;q12), that results in fusion of Ewing's sarcoma and Wilms' tumor (WT1) genes. The authors evaluated 15 DSRCTs and 71 other tumors often considered in the differential diagnosis for immunoreactivity using a polyclonal antibody directed against the WT1 part of the chimeric protein resulting from this translocation. WT1 immunostaining was performed on paraffin material using the WT(C-19) antibody after heat-antigen retrieval. All the DSRCTs (15 of 15, 100%) demonstrated strong WT1 nuclear immunoreactivity. Ten of 14 nephroblastomas (71%) disclosed WT1-positive nuclei in accordance with the staining reported by others, and rare and focal nuclear positivity was detected in two of 17 rhabdomyosarcomas. WT1 immunoreactivity was not observed in Ewing's sarcoma/primitive neuroectodermal tumors (zero of 21, 0%), neuroblastomas (zero of 17, 0%), or rhabdoid tumors of the kidney (zero of two, 0%). In nephroblastoma, differential diagnosis with DSRCT was not difficult: Clinical and morphologic data are not similar for these two entities. The current study validates WT1 immunoreactivity as a useful marker to separate DSRCT from other small round cell tumors.
Cell-induced conformational change in poliovirus: externalization of the amino terminus of VP1 is responsible for liposome binding (1990)

Upon attachment to susceptible cells, poliovirus and a number of other picornaviruses undergo conformational transitions which result in changes in antigenicity, increased protease sensitivity, the loss of the internal capsid protein VP4, and a loss of the ability to attach to cells. These conformationally altered particles have been characterized by using a number of sequence-specific probes, including two proteases, a panel of antiviral monoclonal antibodies, and a panel of antisera against synthetic peptides which correspond to sequences from the capsid protein VP1. With these probes, cell-altered virus is clearly distinguishable from native and heat-inactivated virions. The probes also demonstrate that the cell-induced conformational change alters the accessibility of several regions of the virus. In particular, the amino terminus of VP1, which is entirely internal in the native virion, becomes externalized. Unlike native and heat-inactivated virus, cell-altered virions are able to attach to liposomes. The exposed amino terminus of VP1 is shown to be responsible for liposome attachment. We propose that during infection the amino terminus of VP1 inserts into endosomal membranes and thus plays a role in the mechanism of cell entry.
Ultraviolet Stand-off Raman Measurements Using a Gated Spatial Heterodyne Raman Spectrometer (2016)

A spatial heterodyne Raman spectrometer (SHRS) is evaluated for stand-off Raman measurements in ambient light conditions using both ultraviolet (UV) and visible pulsed lasers with a gated ICCD detector. The wide acceptance angle of the SHRS simplifies optical coupling of the spectrometer to the telescope and does not require precise laser focusing or positioning of the laser on the sample. If the laser beam wanders or loses focus on the sample, as long as it is in the field of view of the SHRS, the Raman signal will still be collected. The SHRS is not overly susceptible to vibrations, and a vibration isolated optical table was not necessary for these measurements. The system performance was assessed by measuring stand-off UV and visible Raman spectra of a wide variety of materials at distances up to 18 m, using 266 nm and 532 nm pulsed lasers, with 12.4 in. and 3.8 in. aperture telescopes, respectively.
Decreased folylpolyglutamate synthetase activity in tumors resistant to fluorouracil-folinic acid treatment: clinical data. (1997)

Thymidylate synthase (TS) is the main target for fluorouracil (FU). Optimal cellular concentrations of reduced folates in polyglutamated forms [via folylpolyglutamate synthetase (FPGS)] are necessary for achieving maximal TS inhibition. The aim of this multicentric prospective study was to analyze the link between clinical response to FU therapy for liver metastases of colorectal carcinoma and tumoral TS and FPGS activities. Forty-four advanced colorectal cancer patients (15 women and 29 men; median age 63, range, 27-78 years) receiving a standard FU-folinic acid protocol were included. A single hepatic tumoral biopsy was obtained systematically at the time of diagnosis. For 24 patients, a biopsy in the primary colon tumor was available. TS and FPGS activities were measured by radioenzymatic assays. Clinical response on hepatic metastases was 1 complete response, 12 partial responses, 14 stabilizations, and 17 progressions. In hepatic biopsies, TS activity (median, 185; range, <10-3111 fmol/min/mg protein) and FPGS activity (median, 1270; range, <400-3730 fmol/min/mg protein) exhibited a wide variability. TS activity in primary tumors (median, 461; range, 35-2565 fmol/min/mg protein) was significantly higher than in hepatic metastases. No difference was observed between primaries and metastases for FPGS. FPGS activity expressed in liver metastases was significantly correlated to that expressed in primaries. The distribution of TS activity in liver metastases was not significantly different between responsive and nonresponsive patients. However, FPGS activity measured in liver metastases was significantly higher in responsive patients (median, 1550 fmol/min/mg protein) than in nonresponsive patients (median, 1100 fmol/min/mg protein). A discriminant analysis revealed that 24 of the 25 patients exhibiting a liver FPGS activity </=1100 fmol/min/mg protein and/or a liver TS >320 fmol/min/mg protein were nonresponding patients. These data establish for the first time the potential importance of tumoral FPGS activity for assessing FU-folinic acid responsiveness in the clinical setting.