gebhart/patrepeval huggingface dataset:
Molecular architecture of a light-harvesting antenna. Comparison of wild type and mutant Synechococcus 6301 phycobilisomes. (1980)

Phycobilisomes of the cyanobacterium Synechococcus 6301 contain C-phycocyanin and allophycocyanin in a molar ratio of approximately 3.8:1, a minor biliprotein, allophycocyanin B, and nonpigmented polypeptides of 75, 33, 30, and 27 kilodaltons. A nitrosoguanidine-induced mutant AN112 produces altered phycobilisomes with the molar ratio of C-phycocyanin to allophycocyanin reduced to approximately 1.4:1 and without any of the 33- and 30-kilodalton polypeptides. The mutant and wild type phycobilisomes contain the same molar amount of the 75- and 27-kilodalton polypeptides relative to allophycocyanin. As seen by electron microscopy, the allophycocyanin-containing core of the mutant and of the wild type phycobilisomes appears the same. In some views of the core, each of the two core units in the mutant particles can be seen to consist of four discs approximately 3 nm thick. In wild type phycobilisomes five or six rods, made up of two to six stacked discs (11.5 X 6 nm) are attached to the core. In the mutant, no such rods are seen; rather, single disc-shaped elements, ranging from two to six in number, are found attached. Spectroscopic measurements show that the assembly form of phycocyanin in the mutant phycobilisomes differs from that in the wild type particles but reveal no difference in the organization of the core elements. These results indicate that the portions of the rod substructures of wild type phycobilisomes, beyond the disc proximal to the core, are made up of phycocyanin and the 33- and 30-kilodalton polypeptides. Emission from phycocyanin is a significant component in the fluorescence from isolated Synechococcus 6301 phycobilisomes and indicates an upper limit of 94% for the efficiency of energy transfer from phycocyanin to allophycocyanin and allophycocyanin B in these particles.
First insert of tau protein is present in all stages of tau pathology in Alzheimer's disease (2005)

A novel monoclonal antibody DC39N1 specific for tau protein N-terminal insert N1 (residues 45-73) was developed. Species analysis revealed that monoclonal antibody DC39N1 did not recognize tau proteins derived from rat, mouse, bovine, swine and rabbit brain tissues and is human tau protein specific. The antibody recognized all and only those human tau isoforms that contain a tau N1 insert. DC39N1 epitope on paired helical filaments from the brain of patients with Alzheimer's disease is phosphorylation independent. Immunohistochemical analysis of Braak stages with novel antibody revealed the presence of tau aminoterminal N1 insert during evolution of neurofibrillary degeneration from early to late stages of Alzheimer's disease.
Efficient Measurement of Quantum Gate Error by Interleaved Randomized Benchmarking (2012)

We describe a scalable experimental protocol for estimating the average error of individual quantum computational gates. This protocol consists of interleaving random Clifford gates between the gate of interest and provides an estimate as well as theoretical bounds for the average error of the gate under test, so long as the average noise variation over all Clifford gates is small. This technique takes into account both state preparation and measurement errors and is scalable in the number of qubits. We apply this protocol to a superconducting qubit system and find a bounded average error of 0.003 [0,0.016] for the single-qubit gates X(π/2) and Y(π/2). These bounded values provide better estimates of the average error than those extracted via quantum process tomography.
Effect of high-intensity statin therapy on atherosclerosis in non-infarct-related coronary arteries (IBIS-4): a serial intravascular ultrasonography study (2014)

High-intensity rosuvastatin therapy over 13 months is associated with regression of coronary atherosclerosis in non-infarct-related arteries without changes in RF-IVUS defined necrotic core or plaque phenotype among STEMI patients.
Fibroblast Growth Factor (FGF)-23 Inhibits Renal Phosphate Reabsorption by Activation of the Mitogen-activated Protein Kinase Pathway (2002)

The homeostasis of the plasma phosphate level is essential for many biological processes including skeletal mineralization. The reabsorption of phosphate in the kidney is a major determinant of the plasma levels of phosphate. Phosphatonin is a hormone-like factor that specifically inhibits phosphate uptake in renal proximal epithelial cells. Recent studies on tumor-induced osteomalacia suggested that phosphatonin was potentially identical to fibroblast growth factor (FGF)-23. However, as purified recombinant FGF-23 could not inhibit phosphate uptake in renal proximal epithelial cells, the mechanism of action of FGF-23 remains to be elucidated. Therefore, we examined the mechanism of action of FGF-23 in cultured renal proximal epithelial cells, opossum kidney cells. FGF-23 was found to require heparin-like molecules for its inhibitory activity on phosphate uptake. FGF-23 binds to the FGF receptor 3c, which is mainly expressed in opossum kidney cells, with high affinity. An inhibitor for tyrosine kinases of the FGF receptor, SU 5402, blocked the activity of FGF-23. FGF-23 activated the mitogen-activated protein kinase (MAPK) pathway, which is the major intracellular signaling pathway of FGF. Inhibitors of the MAPK pathway, PD98059 and SB203580, also blocked the activity of FGF-23. The present findings have revealed a novel MAPK-dependent mechanism of the regulation of phosphate uptake by FGF signaling.
The Structure of Tumor Endothelial Marker 8 (TEM8) Extracellular Domain and Implications for Its Receptor Function for Recognizing Anthrax Toxin (2010)

Anthrax toxin, which is released from the gram-positive bacterium Bacillus anthracis, is composed of three proteins: protective antigen (PA), lethal factor (LF), and edema factor (EF). PA binds a receptor on the surface of the target cell and further assembles into a homo-heptameric pore through which EF and LF translocate into the cytosol. Two distinct cellular receptors for anthrax toxin, TEM8/ANTXR1 and CMG2/ANTXR2, have been identified, and it is known that their extracellular domains bind PA with low and high affinities, respectively. Here, we report the crystal structure of the TEM8 extracellular vWA domain at 1.7 A resolution. The overall structure has a typical integrin fold and is similar to that of the previously published CMG2 structure. In addition, using structure-based mutagenesis, we demonstrate that the putative interface region of TEM8 with PA (consisting of residues 56, 57, and 154-160) is responsible for the PA-binding affinity differences between the two receptors. In particular, Leu56 was shown to be a key factor for the lower affinity of TEM8 towards PA compared with CMG2. Because of its high affinity for PA and low expression in normal tissues, an isolated extracellular vWA domain of the L56A TEM8 variant may serve as a potent antitoxin and a potential therapeutic treatment for anthrax infection. Moreover, as TEM8 is often over-expressed in tumor cells, our TEM8 crystal structure may provide new insights into how to design PA mutants that preferentially target tumor cells.
Even Viruses Can Learn to Cope with Stress (1998)

When a virus infects a cell, cellular defense mechanisms are activated, sometimes even causing cell death in an effort to stem the infection. As McFadden explains in his commentary, the virus in turn marshals its own countermeasures, striving to keep the cell alive so the virus can replicate and spread. A report in this week's issue by [ Schisler et al .][1] shows how one of these countermeasures--synthesis of glutathione synthase, which protects cells against oxidative damage--is used by molluscum contagiosum virus and synthesized by a unique translation control mechanism for selenoproteins.

 [1]: http://www.sciencemag.org/cgi/content/short/279/5347/102
Phytochromes and Shade-avoidance Responses in Plants (2005)

The Briefing covers: (a) the shade-avoidance syndrome in higher plants; (b) the adaptive significance of shade avoidance in natural light environments; (c) phytochrome regulation of shade-avoidance responses; (d) the role of blue light signals in shade avoidance; (e) gating of rapid shade-avoidance responses by the circadian clock; (f) potential signalling components and future perspectives.
Cell-Cycle Associated Transcriptional Regulation of Ribonucleotide Reductase in L1210 Leukemia Cells and Drug-Resistant Variants (1991)

Previous studies from this laboratory have shown that the steady-state levels of the mRNA for the non-heme iron (NHI) subunit of ribonucleotide reductase were markedly elevated in hydroxyurea-resistant L1210 cell lines with minimal changes in the mRNA levels for the effector-binding (EB) subunit. In the present study, wild-type L1210 cells and their drug-resistant variants [hydroxyurea-resistant (HU-7); deoxyadenosine-resistant (Y-8); and deoxyadenosine/pyrazoloimidazole-resistant (ED2)] were synchronized by EGTA treatment in the G0/G1-phase of the cell cycle. Upon the addition of CaCl2, the cells reentered the cell cycle. The steady-state levels and the transcriptional rates of the mRNAs for the EB subunit and glyceraldehyde-3-phosphate dehydrogenase were measured and found to be similar in the drug-resistant variants compared to the wild-type cells. While the steady-state level of the mRNA for the NHI subunit was increased 35-fold in the HU-7 cell line, the transcription rate was increased only 7-fold. The increase in the transcription rate did not account for the large increase in the steady-state level. These data indicate that the increased steady-state level of the mRNA for the NHI subunit in the HU-7 L1210 cell line was not due to cell-cycle differences and that post-transcriptional processing and/or stability may play a role as well.
Identification of the FKS1 gene of Candida albicans as the essential target of 1,3-beta-D-glucan synthase inhibitors (1997)

Pneumocandins and echinocandins are fungicidal antibiotics, currently in clinical development, that inhibit 1,3-beta-D-glucan synthase (GS) in several human fungal pathogens. We have identified a gene from the diploid organism Candida albicans that encodes a target of these inhibitors. A 2.1-kb portion of this gene, designated CaFKS1, has significant homology to the Saccharomyces cerevisiae FKS1 and FKS2 genes, which encode partially functionally redundant subunits of GS. To evaluate the role of CaFkslp in susceptibility to echinocandins, we disrupted CaFKS1 on one homolog each of the spontaneous pneumocandin-resistant C. albicans mutants CAI4R1, NR2, NR3, and NR4. These mutants had been selected previously on agar plates containing the pneumocandin L-733,560. The clones derived from this transformation were either resistant (Ech[r]) or fully sensitive (Ech[s]) to inhibition by L-733,560 in both liquid broth microdilution and in vitro GS assays. The site of plasmid insertion in the transformants was mapped by Southern blot analysis, using restriction site polymorphisms in the CaFKS1 gene to distinguish between the two alleles (designated CaFKS1h and CaFKS1b). For strains CAI4R1 and NR2, the CaFKS1b allele was disrupted in each Ech(r) transformant; for strain NR4, CaFKS1h was disrupted in each Ech(r) transformant. We conclude that (i) strains CAI4R1, NR2, and NR4 are heterozygous for a dominant or semidominant pneumocandin resistance mutation at CaFKS1, (ii) drug resistance mutations can occur in either CaFKS1 allele, and (iii) CaFks1p is a target of the echinocandins. For transformants of strain NR3, all the clones we analyzed were uniformly Ech(r), and only the CaFKS1h allele, either in disrupted or wild-type form, was detected on genomic Southern blots. We believe gene conversion at the CaFKS1 locus may have produced two Cafks1h alleles that each contain an Ech(r) mutation. Transformants derived from the mutants were analyzed for susceptibility to pneumocandin treatment in a mouse model of disseminated candidiasis. Strains heterozygous for the resistant allele (i.e., C. albicans CAI4R1, NR2, and NR4) were moderately resistant to treatment, while strains without a functional Ech(s) allele (i.e., strain NR3 and derivatives of strain CAI4R1 with the disruption plasmid integrated in the Ech[s] allele) displayed strong in vivo echinocandin resistance. Finally, we were unable to inactivate both alleles at CaFKS1 by two-step integrative disruption, suggesting that CaFks1p is likely to be an essential protein in C. albicans.
Impact of Word Segmentation Errors on Automatic Chinese Text Classification (2012)

In this paper, several sets of experiments were carried out to study the impact of word segmentation errors on automatic Chinese text classification. Comparison experiment of four word-based approaches was first carried out and the results show that the performance was significantly reduced when using automatic word segmentation instead of manual word segmentation which means errors caused by automatic word segmentation have an obvious impact on classification performance. We further conducted the experiment using character-based approach (N-gram). Although N-gram approach produces a large number of ambiguous words, the results show that it performed better than automatic word segmentation.
A retro-inverso peptide corresponding to the GH loop of foot-and-mouth disease virus elicits high levels of long-lasting protective neutralizing antibodies (1997)

Peptides corresponding to the immunodominant loop located at residues 135-158 on capsid protein VP1 of foot-and-mouth disease virus (FMDV) generally elicit high levels of anti-peptide and virus-neutralizing antibodies. In some instances, however, the level of neutralizing antibodies is low or even negligible, even though the level of anti-peptide antibodies is high. We have shown previously that the antigenic activity of peptide 141-159 of VP1 of a variant of serotype A can be mimicked by a retro-inverso (all-D retro or retroenantio) peptide analogue. This retro-inverso analogue induced greater and longer-lasting antibody titers than did the corresponding L-peptide. We now show that a single inoculation of the retro-inverso analogue elicits high levels of neutralizing antibodies that persist longer than those induced against the corresponding L-peptide and confer substantial protection in guinea pigs challenged with the cognate virus. In view of the high stability to proteases of retro-inverso peptide analogues and their enhanced immunogenicity, these results have practical relevance in designing potential peptide vaccines.
Digital Isothermal Quantification of Nucleic Acids via Simultaneous Chemical Initiation of Recombinase Polymerase Amplification Reactions on SlipChip (2011)

In this paper, digital quantitative detection of nucleic acids was achieved at the single-molecule level by chemical initiation of over one thousand sequence-specific, nanoliter isothermal amplification reactions in parallel. Digital polymerase chain reaction (digital PCR), a method used for quantification of nucleic acids, counts the presence or absence of amplification of individual molecules. However, it still requires temperature cycling, which is undesirable under resource-limited conditions. This makes isothermal methods for nucleic acid amplification, such as recombinase polymerase amplification (RPA), more attractive. A microfluidic digital RPA SlipChip is described here for simultaneous initiation of over one thousand nL-scale RPA reactions by adding a chemical initiator to each reaction compartment with a simple slipping step after instrument-free pipet loading. Two designs of the SlipChip, two-step slipping and one-step slipping, were validated using digital RPA. By using the digital RPA SlipChip, false-positive results from preinitiation of the RPA amplification reaction before incubation were eliminated. End point fluorescence readout was used for "yes or no" digital quantification. The performance of digital RPA in a SlipChip was validated by amplifying and counting single molecules of the target nucleic acid, methicillin-resistant Staphylococcus aureus (MRSA) genomic DNA. The digital RPA on SlipChip was also tolerant to fluctuations of the incubation temperature (37-42 °C), and its performance was comparable to digital PCR on the same SlipChip design. The digital RPA SlipChip provides a simple method to quantify nucleic acids without requiring thermal cycling or kinetic measurements, with potential applications in diagnostics and environmental monitoring under resource-limited settings. The ability to initiate thousands of chemical reactions in parallel on the nanoliter scale using solvent-resistant glass devices is likely to be useful for a broader range of applications.
Effects of Thioamide Substitutions on the Conformation and Stability of α- and 310-Helices (2002)

Thiopeptides, formed by replacing the amide oxygen atom with a sp(2) sulfur atom, are useful in protein engineering and drug design because they confer resistance to enzymatic degradation and are predicted to be more rigid. This report describes our free molecular dynamics simulations with explicit water and free energy calculations on the effects of thio substitutions on the conformation of alpha-helices, 3(10)-helices, and their relative stability. The most prominent structural effect of thio substitution is the increase in the hydrogen bond distance from 2.1 A for normal peptides to 2.7 A for thiopeptides. To accommodate for the longer C[double bond]S...H-N hydrogen bond, the (phi, psi) dihedral angles of the alpha-helix changed from (-66 degrees, -42 degrees) to (-68 degrees, -38 degrees), and the rise per turn increased from 5.5 to 6.3 A. For 3(10)-helices, the (phi, psi) dihedral angles (-60 degrees, -20 degrees) and rise per turn (6.0 A) changed to (-66 degrees, -12 degrees) and 6.8 A, respectively. In terms of relative stability, the most prominent change upon thio substitution is the decrease in the free energy difference, Delta A(alpha --> 3(10)), from 14 to 3.5 kcal/mol. Therefore, normal peptides are less likely to form 3(10)-helix than are thiopeptides. Component analysis of the Delta A(alpha --> 3(10)) reviews that the entropy advantage of the 3(10)-helix for both Ac-Ala(10)-NHMe and Act-Alat(10)-NHMe is attributed to the 3(10)-helix being more flexible than the alpha-helix. Interestingly, upon thio substitution, this differential flexibility is even more apparent because the alpha-helix conformation of Act-Alat(10)-NHMe becomes more rigid due to the bulkier sulfur atom.
Autocrine growth factors in human periodontal ligament cells cultured on enamel matrix derivative (2001)

Cultured PDL cells exposed to EMD increase attachment rate, growth rate and metabolism, and subsequently release several growth factors into the medium. The cellular interaction with EMD generates an intracellular cAMP signal, after which cells secrete TGF-beta1, IL-6 and PDGF AB. Epithelial cell growth however, is inhibited by the same signal. This suggest that EMD favours mesenchymal cell growth over epithelium, and that autocrine growth factors released by PDL cells exposed to EMD contribute to periodontal healing and regeneration in a process mimicking natural root development.
Postprandial peristalsis in the human duodenum (1998)

MMC-related retroperistalsis is a cyclical phenomenon in the duodenum linked to phase III. The aim of this study was to elucidate the direction of propagation of juxtapyloric duodenal pressure waves in the postprandial state in healthy humans and to compare with the contractions in the interdigestive phase II. Antroduodenal manometry was performed in 11 healthy subjects. Individual pressure waves propagating along a 6-cm duodenal segment were analysed with respect to the proportions of antegrade and retrograde propagation in the four duodenal subsegments (D1-D2) to (D4-D5), each subsegment being 15 mm. A test meal was given 30 min after a phase III had passed and motility recording continued for 60 min after the meal. During both the first and the second 30-min period of postprandial recording the proportion of retrograde pressure waves was larger just distal to the pylorus, (D1-D2), 40% (23-68) and 50% (23-68), respectively, compared to the distal part, (D4-D5), of the duodenal segment, 29% (12-30) and 10% (10-24), respectively (P < 0.05 and 0.01). In contrast, during late phase II of the interdigestive state antegrade pressure waves predominated in all four duodenal subsegments. We conclude that in the postprandial state a high proportion of the duodenal pressure waves (40-50%) is retrograde in the immediate juxtapyloric area while antegrade contractions predominate at a distance 5-6 cm distal to the pylorus. These manometric data together with recent observations of postprandial transpyloric liquid flow, indicate that retrograde duodenogastric propelling of contents may be an important determinant for the gastric emptying rate.
In Vitro Endothelialization of Carbon-Coated Dacron Vascular Grafts (1992)

Physical vapour deposition is used to coat vascular prostheses with pyrolytic carbon. This coating may facilitate the development of an endothelial monolayer in grafts implanted in laboratory animals. This in vitro study compared the adherence and growth of cultured porcine aortic endothelial cells (EC) seeded in vitro on carbon-coated Dacron, to uncoated prostheses. The cells were incubated at 5 x 10(4) cells/cm2. Progress was monitored at different times (TO + 2 hours, D 1, D 4, D 8) by microscopic observation, when cell counts were made; and by scanning electronic microscopy (SEM) to evaluate morphological EC-graft interactions. Cell adherence was independent of the carbon coating but cellular growth occurred only on carbon-coated Dacron. The SEM observations showed both the shape of the adherent cells, which were rounded on uncoated Dacron and extensively spread on carbon-coated prostheses, and the morphology of the carbon coating.
Phosphinic peptide inhibitors as tools in the study of the function of zinc metallopeptidases (2000)

The development of the combinatorial chemistry of phosphinic peptides has led to the discovery of both highly potent and selective inhibitors of various zinc metalloproteinases. Several properties of these compounds are reviewed, supporting the view that this class of inhibitors should represent useful tools for probing several aspects of the function of this broad family of proteases in vivo.
UK‐78,282, a novel piperidine compound that potently blocks the Kv1.3 voltage‐gated potassium channel and inhibits human T cell activation (1999)

1. UK-78,282, a novel piperidine blocker of the T lymphocyte voltage-gated K+ channel, Kv1.3, was discovered by screening a large compound file using a high-throughput 86Rb efflux assay. This compound blocks Kv1.3 with a IC50 of approximately 200 nM and 1:1 stoichiometry. A closely related compound, CP-190,325, containing a benzyl moiety in place of the benzhydryl in UK-78,282, is significantly less potent. 2 Three lines of evidence indicate that UK-78,282 inhibits Kv1.3 in a use-dependent manner by preferentially blocking and binding to the C-type inactivated state of the channel. Increasing the fraction of inactivated channels by holding the membrane potential at - 50 mV enhances the channel's sensitivity to UK-78,282. Decreasing the number of inactivated channels by exposure to approximately 160 mM external K+ decreases the sensitivity to UK-78,282. Mutations that alter the rate of C-type inactivation also change the channel's sensitivity to UK-78,282 and there is a direct correlation between tau(h) and IC50 values. 3. Competition experiments suggest that UK-78,282 binds to residues at the inner surface of the channel overlapping the site of action of verapamil. Internal tetraethylammonium and external charybdotoxin do not compete UK-78,282's action on the channel. 4. UK-78,282 displays marked selectivity for Kv1.3 over several other closely related K+ channels, the only exception being the rapidly inactivating voltage-gated K+ channel, Kv1.4. 5. UK-78,282 effectively suppresses human T-lymphocyte activation.