gebhart/patrepeval huggingface dataset:
Structure of ricin B‐chain at 2.5 Å resolution (1991)

The heterodimeric plant toxin ricin has been refined to 2.5 A resolution. The B-chain lectin (RTB) is described in detail. The protein has two major domains, each of which has a galactose binding site. RTB has no regular secondary structure but displays several omega loops. Each RTB domain is made of three copies of a primitive 40 residue folding unit, which pack around a pseudo threefold axis. In each domain, galactose binds in a shallow cleft formed by a three residue peptide kink on the bottom and an aromatic ring on the top. At the back of the cleft, an aspartate forms hydrogen bonds to the C3 and C4 hydroxyls of galactose, whereas a glutamine bonds to the C4 alcohol, helping to define specific epimer binding. In addition to analyzing the sugar binding mechanism, the assembly of subdomain units around the pseudo threefold axis of each domain is described. The subdomains contribute conserved Trp, Leu, and Ile residues to a compact central hydrophobic core. This tight threefold binding probably drives the peptide folding and stabilizes the protein structure.
Paradoxically enhanced glucose production during exercise in humans with blocked glycolysis caused by muscle phosphofructokinase deficiency (1996)

Muscle phosphofructokinase deficiency (PFKD) is characterized by exercise intolerance due to the enzymatic block in muscle glycolysis. Glucose infusion increases exertional fatigue in these patients, probably by decreasing the availability of free fatty acids (FFA) and ketones, which play a crucial role in ATP production during exercise in PFKD. This suggests that a lower than normal hepatic glucose production would be appropriate during exercise in PFKD. To investigate glucoregulation in PFKD, we measured glucose turnover and hormonal and metabolic responses to 20 minutes of cycle exercise at near maximal effort in three patients with PFKD and in healthy matched controls studied at the same absolute (A, 15 to 30 Watts) and relative (R, 35 to 80 Watts, matched heart rates) work load as the patients. During exercise, mean glucose production was higher in all patients versus controls (30 +/- 4 versus A: 18 +/- 2 and R: 20 +/- 1 mumol.min-1.kg-1). Mean glucose utilization during exercise was similar in patients and controls working at the same relative work load and higher than in controls at the low work load. Exercise-induced increases in arterialized blood were higher in all patients for glucose, FFA, growth hormone, glucagon, and norepinephrine. Plasma alanine and lactate always decreased during exercise in patients and consistently increased in controls. In conclusion, an enhanced neuroendocrine response and a paradoxically exaggerated mobilization of glucose occurs during exercise in PFKD. The responses are probably initiated by neural feedback elicited by disturbances in local muscle metabolism. The responses promote delivery of oxidizable fat to muscle, but at the expense of accumulation and futile cycling of glucose.
A Seeded Image Segmentation Framework Unifying Graph Cuts And Random Walker Which Yields A New Algorithm (2007)

In this work, we present a common framework for seeded image segmentation algorithms that yields two of the leading methods as special cases - The Graph Cuts and the Random Walker algorithms. The formulation of this common framework naturally suggests a new, third, algorithm that we develop here. Specifically, the former algorithms may be shown to minimize a certain energy with respect to either an 𝓁 <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">1</sub> or an 𝓁 <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> norm. Here, we explore the segmentation algorithm defined by an 𝓁 <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">∞</sub> norm, provide a method for the optimization and show that the resulting algorithm produces an accurate segmentation that demonstrates greater stability with respect to the number of seeds employed than either the Graph Cuts or Random Walker methods.
Monocyte Chemoattractant Protein-1 but Not Tumor Necrosis Factor-α Is Correlated With Monocyte Infiltration in Mouse Lipid Lesions (1999)

From this we conclude that ICAM-1, VCAM-1, TNF-alpha, and MIP-1alpha may all be necessary for vascular monocyte recruitment in vivo, but they cannot be sufficient. Monocyte chemoattractant protein-1 (MCP-1) protein was undetectable in the vessel wall taken from apo(a) transgenic mice fed a high fat diet compared with high expression in mice with lipid lesions (C57BL/6 and apoE knockout mice). Therefore elevated expression of MCP-1 but not TNF-alpha, MIP-1alpha, ICAM-1, or VCAM-1 is correlated with vascular macrophage accumulation. To test the hypothesis that monocyte infiltration during atherogenesis is MCP-1 dependent, it will be necessary to develop specific pharmacological inhibitors of MCP-1 activity.
Luminescent hyperbolic metasurfaces (2017)

When engineered on scales much smaller than the operating wavelength, metal-semiconductor nanostructures exhibit properties unobtainable in nature. Namely, a uniaxial optical metamaterial described by a hyperbolic dispersion relation can simultaneously behave as a reflective metal and an absorptive or emissive semiconductor for electromagnetic waves with orthogonal linear polarization states. Using an unconventional multilayer architecture, we demonstrate luminescent hyperbolic metasurfaces, wherein distributed semiconducting quantum wells display extreme absorption and emission polarization anisotropy. Through normally incident micro-photoluminescence measurements, we observe absorption anisotropies greater than a factor of 10 and degree-of-linear polarization of emission >0.9. We observe the modification of emission spectra and, by incorporating wavelength-scale gratings, show a controlled reduction of polarization anisotropy. We verify hyperbolic dispersion with numerical simulations that model the metasurface as a composite nanoscale structure and according to the effective medium approximation. Finally, we experimentally demonstrate >350% emission intensity enhancement relative to the bare semiconducting quantum wells.
Controlling the type I and type II errors in mapping quantitative trait loci. (1994)

Although the interval mapping method is widely used for mapping quantitative trait loci (QTLs), it is not very well suited for mapping multiple QTLs. Here, we present the results of a computer simulation to study the application of exact and approximate models for multiple QTLs. In particular, we focus on an automatic two-stage procedure in which in the first stage "important" markers are selected in multiple regression on markers. In the second stage a QTL is moved along the chromosomes by using the preselected markers as cofactors, except for the markers flanking the interval under study. A refined procedure for cases with large numbers of marker cofactors is described. Our approach will be called MQM mapping, where MQM is an acronym for "multiple-QTL models" as well as for "marker-QTL-marker." Our simulation work demonstrates the great advantage of MQM mapping compared to interval mapping in reducing the chance of a type I error (i.e., a QTL is indicated at a location where actually no QTL is present) and in reducing the chance of a type II error (i.e., a QTL is not detected).
MICROBIAL AROMATIZATION OF 19-HYDROXYME- THYL EPIDEHYDROANDROSTERONE ACETATE BY COR YNEBACTERIUM SIMPLEX (1983)

Microbial aromatization of 19-hydroxymetbyl-epidehydroandrosterone acetate(4a)with Corynebacterium simplex afforded estrone(1) in ca.60%, while using the free alcohol 4b as substrate, the yield of estrone was increased to 74%
α2 Adrenoceptor Agonists as Potential Analgesic Agents. 2. Discovery of 4-(4-Imidazo)-1,3-dimethyl-6,7-dihydrothianaphthene as a High-Affinity Ligand for the α2D Adrenergic Receptor (2000)

ADVERTISEMENT RETURN TO ISSUEPREVAddition/CorrectionORIGINAL ARTICLEThis notice is a correctionα2 Adrenoceptor Agonists as Potential Analgesic Agents. 2. Discovery of 4-(4-Imidazo)-1,3-dimethyl-6,7-dihydrothianaphthene as a High-Affinity Ligand for the α2D Adrenergic ReceptorTina M. Ross, Michele C. Jetter, Mark E. McDonnell, Robert E. Boyd, Charlene D. Connelly, Rebecca P. Martinez, Martin A. Lewis, Ellen E. Codd, Robert B. Raffa, and Allen B. ReitzView Author Information Drug Discovery Division, The R. W. Johnson Pharmaceutical Research Institute, Spring House, Pennsylvania 19477 Cite this: J. Med. Chem. 2000, 43, 7, 1423–1426Publication Date (Web):March 24, 2000Publication History Received15 November 1999Published online24 March 2000Published inissue 6 April 2000https://pubs.acs.org/doi/10.1021/jm000128rhttps://doi.org/10.1021/jm000128rcorrectionACS PublicationsCopyright © 2000 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 Views950Altmetric-Citations6LEARN 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 (91 KB) Get e-AlertscloseSupporting Info ()»Supporting Information Supporting Information Get e-Alerts
Characterisation of secondary metabolites associated with neutrophil apoptosis (1996)

We studied changes in secondary metabolites in human neutrophils undergoing constitutive or tumour necrosis factor (TNFalpha) stimulated apoptosis by a combination of high-performance liquid chromatography (HPLC) and NMR spectroscopy. Our results show that in contrast to freshly isolated neutrophils, neutrophil cells aged for 20 h in vitro had marked differences in the levels of a number of endogenous metabolites including lactate, amino acids and phosphocholine (PCho). There was no change in the concentration of taurine or glutamate and the ATP/ADP ratio was not affected. Levels of glutamine and lactate actually decreased. Identical changes were also observed in neutrophils stimulated to undergo apoptosis over a shorter time period (6 h) in the presence of TNFalpha and the phosphatidylinositol-3-kinase inhibitor wortmannin (WM). The changes in the concentration of PCho suggest possible activation of phospholipase associated with apoptosis or a selective failure of phosphatidycholine synthesis. The increased levels of apoptosis obtained with WM+TNFalpha, compared to TNFalpha by itself, suggest a synergistic effect by these compounds. The acceleration in rate of apoptosis probably arises from suppression by WM of pathway(s) that normally delay the onset of apoptosis. Changes in PCho and other endogenous metabolites, if proven to be characteristic of apoptosis in other cell systems, may permit non-invasive quantification of apoptosis. '
Cutting Edge: Selective Usage of Chemokine Receptors by Plasmacytoid Dendritic Cells (2001)

The existence of dendritic cell (DC) subsets is firmly established, but their trafficking properties are virtually unknown. In this study, we show that myeloid (M-DCs) and plasmacytoid (P-DCs) DCs isolated from human blood differ widely in the capacity to migrate to chemotactic stimuli. The pattern of chemokine receptors expressed by blood M-DCs and P-DCs, with the exception of CCR7, is similar. However, most chemokine receptors of P-DCs, in particular those specific for inflammatory chemokines and classical chemotactic agonists, are not functional in circulating cells. Following maturation induced by CD40 ligation, the receptors for inflammatory chemokines are down-regulated, and CCR7 on P-DCs becomes coupled to migration. The drastically impaired capacity of blood P-DCs to migrate in response to inflammatory chemotactic signals contrasts with the response to lymph node-homing chemokines, indicating a propensity to migrate to secondary lymphoid organs rather than to sites of inflammation.
Use of a Three‐Dimensional, Nonfluoroscopic Mapping System for Catheter Ablation of Typical Atrial Flutter (1998)

Recent studies have shown that typical atrial flutter (AFL) results from right atrial reentry around the tricuspid annulus (TA), constrained between the TA and crista terminalis (CT) on the free-wall and the TA and eustachian ridge (ER) on the septum. Creation of a complete line of conduction block across the subeustachian isthmus, between the TA and ER, eliminates AFL. The accuracy of fluoroscopy in localizing the anatomical boundaries and previous radiofrequency application sites is limited. This article describes an approach for utilizing a new three-dimensional nonfluoroscopic electroanatomical mapping system (CARTO) to examine the global right atrial activation pattern in patients during AFL, localize the anatomical boundaries, and create a complete line of conduction block by ablation across the subeustachian isthmus. During AFL, the locations of CT and ER are identified by double atrial potentials recorded along the intercaval region and between the inferior vena cava and coronary sinus ostium, respectively. Radiofrequency ablation across the subeustachian isthmus is performed during coronary sinus pacing. Beginning at TA, the ablation electrode is moved toward ER in 2-3 mm increments. Each movement is marked on the right atrial map to visualize the ablation line. In the event of residual conduction across the ablation line, defects in the ablation line are located by mapping along the previous ablation sites guided by CARTO system to locate the transition from the double atrial potentials (indicating block) to a single atrial potential (indicating conduction). Radiofrequency ablation to the site showing the single atrial potential along the ablation line produces complete conduction block across the subeustachian isthmus. In conclusion, the new electroanatomical mapping system allows precise 3-D localization of the anatomical boundaries of the AFL reentrant circuit, and facilitates ablation by accurately locating defects in the ablation line.
Post-Silicon Bug Localization in Processors Using Instruction Footprint Recording and Analysis (IFRA) (2009)

Instruction Footprint Recording and Analysis (IFRA) overcomes challenges associated with an expensive step in post-silicon validation of processors-pinpointing the bug location and the instruction sequence that exposes the bug from a system failure. On-chip recorders collect instruction footprints (information about flows of instructions and what the instructions did as they passed through various design blocks) during the normal operation of the processor in a post-silicon system validation setup. Upon system failure, the recorded information is scanned out and analyzed offline for bug localization. Special self-consistency-based program analysis techniques, together with the test program binary of the application executed during post-silicon validation, are used for this purpose. Major benefits of using IFRA over traditional techniques for post-silicon bug localization are as follows: 1) it does not require full system-level reproduction of bugs, and 2) it does not require full system-level simulation. Simulation results on a complex superscalar processor demonstrate that IFRA is effective in accurately localizing electrical bugs with very little impact on overall chip area.
The Specific Binding of Biebrich Scarlet to the Active Site of α-Chymotrypsin (1967)

This paper reports on the presence of a strong binding site for the dye Biebrich Scarlet, (6-[Z-hydroxy-l-naphthyl]azo)-3,4'-azodibenzene sulfonic acid, on cr-chymotrypsin.The 1: 1 protein-dye complex is characterized by a Kdiss of 8.8 f 0.1 X 10U5 M in 0.1 M phosphate buffer at pH 7.6 and W'.Complex formation is associated with a red shift in the visible spectrum of the dye, and a characteristic difference spectrum with a maximum at 550 rnp and a Ae, of 11,700.The dye is displaced from chymotrypsin by substrates, competitive inhibitors, and active site reagents, such as N-trans-cinnamoylimidazole and phenyhnethanesulfonylfluoride.Thus, the binding site for Biebrich Scarlet overlaps the active site region in cY-chymotrypsin.The dye does not bind strongly to chymotrypsinogen, or to trypsin, and shows no significant spectral perturbation in the presence of these proteins, under the conditions used in this study.
Detection of a potent humoral response associated with immune-induced remission of chronic myelogenous leukemia (2000)

The effectiveness of donor-lymphocyte infusion (DLI) for treatment of relapsed chronic myelogenous leukemia (CML) after allogeneic bone marrow transplantation is a clear demonstration of the graft-versus-leukemia (GVL) effect. T cells are critical mediators of GVL, but the antigenic targets of this response are unknown. To determine whether patients who respond to DLI also develop B-cell immunity to CML-associated antigens, we analyzed sera from three patients with relapsed CML who achieved a complete molecular remission after infusion of donor T cells. Sera from these individuals recognized 13 distinct gene products represented in a CML-derived cDNA library. Two proteins, Jkappa-recombination signal-binding protein (RBP-Jkappa) and related adhesion focal tyrosine kinase (RAFTK), were recognized by sera from three of 19 DLI responders. None of these antigens were recognized by sera from healthy donors or patients with chronic graft-versus-host disease. Four gene products were recognized by sera from CML patients treated with hydroxyurea and nine were detected by sera from CML patients who responded to IFN-alpha. Antibody titers specific for RAFTK, but not for RBP-Jkappa, were found to be temporally associated with the response to DLI. These results demonstrate that patients who respond to DLI generate potent antibody responses to CML-associated antigens, suggesting the development of coordinated T- and B-cell immunity. The characterization of B cell-defined antigens may help identify clinically relevant targets of the GVL response in vivo.
Synthesis ofβ3-Homophenylalanine-Derived Amino Acids and Peptides bySuzuki Coupling in Solution and on Solid Support (2006)

β-Peptides and, to a certain extent, also mixed α,β-peptides, are resistant to degradation by a variety of proteolytic enzymes that rapidly degrade natural α-peptides. This is one of many characteristics that make β-peptides an attractive class of compounds for drug-discovery studies. On the other hand, modern organometallic reactions such as the Suzuki–Miyaura cross-coupling have become standard tools in industry laboratories to derivatize side chains of α-peptidic compounds to build up libraries of unnatural peptides. Combining both features, we prepared (4-bromo)-β3-homophenylalanine derivatives 3–5 and 12 as precursors for Suzuki–Miyaura couplings. From these bromo compounds, we synthesized biaryl-substituted β-homoamino acids 6, and analogs 13 and 15 of the anti-AIDS drug Saquinavir.
Comparison between NRZ and RZ signal formats for in-line amplifier transmission in the zero-dispersion regime (1998)

Nonreturn-to-zero (NRZ) and return-to-zero (RZ) signal formats are experimentally and numerically compared for single-channel long-distance transmission in an in-line amplifier system with dispersion management providing average zero dispersion and local nonzero dispersion at an interval equal to the in-line amplifier spacing. Among a 20-ps RZ signal, a 40-ps RZ signal, and an NRZ signal transmitted in 10 Gb/s straight-line experiments, the last signal achieves the longest transmission distance of 6000 km while the others are limited to 4400 km. Numerical simulations explain these results well and show that, along with linear amplified spontaneous emission (ASE) accumulation, signal waveform distortion due to the combined effect of higher order group-velocity dispersion (GVD) and self-phase modulation (SPM) dominates the performance. Nonlinear optical noise enhancement is not obvious because of the fiber dispersion arrangement. Signals with large pulse widths are less affected by the combined effect, while small-width signals yield superior initial signal-to-noise ratio (SNR) as determined by optical noise. A detailed simulation indicates that a pulse width of about 60 ps is optimum for long distance transmission under the fiber dispersion arranged in this paper.
Putrescine uptake and release by colon cancer cells (1989)

We have investigated the uptake and release of [3H]putrescine by a human colon adenocarcinoma cell line (LoVo) maintained on filter inserts. This culture system permits the cells to develop morphological polarity and provides separate access to the basolateral and apical surfaces of the cells. [3H]putrescine was taken up more readily by the basolateral than by the apical side of the cells. [3H]putrescine uptake could be stimulated greater than 300 times by either 10 mM asparagine or 10% fetal bovine serum. [3H]putrescine was accumulated to a concentration gradient of approximately 300-fold; uptake could be inhibited 50% by 7.5 microM unlabeled putrescine and was not dependent on Na+. The release of [3H]putrescine into the apical medium was inhibited by asparagine or fetal bovine serum. Usually, less than one-thousandth of the [3H]putrescine taken up into the cells was released into the apical medium. Release of [3H]putrescine did not correspond to the accumulation of [14C]-inulin in the apical medium. For these reasons we concluded that putrescine release was not simply passive leakage but was responsive to intracellular demand. The [3H]putrescine taken up by the cells as well as that released into the apical medium was greater than 90% unmetabolized at 4h.
Transcranial Alternating Current Stimulation Affects Decision Making (2012)

GENERAL COMMENTARY article Front. Syst. Neurosci., 25 May 2012 | https://doi.org/10.3389/fnsys.2012.00039
Different thermostabilities of FLP and Cre recombinases: implications for applied site-specific recombination (1996)

Genomic manipulations using site-specific recombinases rely on their applied characteristics in living systems. To understand their applied properties so that they can be optimally deployed, we compared the recombinases FLP and Cre in two assays. In both Escherichia coli and in vitro, FLP shows a different temperature optimum than Cre. FLP is more thermolabile, having an optimum near 30 degrees C and little detectable activity above 39 degrees C. Cre is optimally efficient at 37 degrees C and above. Consistent with FLP thermolability, recombination in a mammalian cell line mediated by a ligand- regulated FLP-androgen receptor fusion protein is more efficient at 35 degrees C than at higher temperatures. We also document a mutation in a commercially available FLP plasmid (FLP-F70L) which renders this recombinase even more thermolabile. The different temperature optima of FLP, FLP-F70L and Cre influence their strategies of usage. Our results recommend the use of Cre for applications in mice that require efficient recombination. The thermolabilities of FLP and FLP-F70L can be usefully exploited for gain of function and cell culture applications.