gebhart/patrepeval huggingface dataset:
Robust Neutralizing Antibodies Elicited by HIV-1 JRFL Envelope Glycoprotein Trimers in Nonhuman Primates (2013)

Host cell-mediated proteolytic cleavage of the human immunodeficiency virus type 1 (HIV-1) gp160 precursor glycoprotein into gp120 and gp41 subunits is required to generate fusion-competent envelope glycoprotein (Env) spikes. The gp120-directed broadly neutralizing monoclonal antibodies (bNabs) isolated from HIV-infected individuals efficiently recognize fully cleaved JRFL Env spikes; however, nonneutralizing gp120-directed monoclonal antibodies isolated from infected or vaccinated subjects recognize only uncleaved JRFL spikes. Therefore, as an immunogen, cleaved spikes that selectively present desired neutralizing epitopes to B cells may elicit cross-reactive neutralizing antibodies. Accordingly, we inoculated nonhuman primates (NHPs) with plasmid DNA encoding transmembrane-anchored, cleaved JRFL Env or by electroporation (EP). Priming with DNA expressing soluble, uncleaved gp140 trimers was included as a comparative experimental group of NHPs. DNA inoculation was followed by boosts with soluble JRFL gp140 trimers, and control NHPs were inoculated with soluble JRFL protein trimers without DNA priming. In the TZM-bl assay, elicitation of neutralizing antibodies against HIV-1 tier 1 isolates was robust following the protein boost. Neutralization of tier 2 isolates was detected, but only in animals primed with plasmid DNA and boosted with trimeric protein. Using the more sensitive A3R5 assay, consistent neutralization of both clade B and C tier 2 isolates was detected from all regimens assessed in the current study, exceeding levels achieved by our previous vaccine regimens in primates. Together, these data suggest a potential advantage of B cell priming followed by a rest interval and protein boosting to present JRFL Env spikes to the immune system to better generate HIV-1 cross-clade neutralizing antibodies.
Crucial Role of the CCL2/CCR2 Axis in Neointimal Hyperplasia After Arterial Injury in Hyperlipidemic Mice Involves Early Monocyte Recruitment and CCL2 Presentation on Platelets (2004)

Monocyte chemoattractant protein-1 (also known as CC chemokine ligand 2 [CCL2]) and its receptor CC chemokine receptor 2 (CCR2) play a central role in the inflammatory response and neointimal formation after vascular injury. In the context of hyperlipidemia, this appears to involve neointimal monocyte infiltration. Hence, we investigated the function of the CCL2/CCR2 axis in early monocyte recruitment to injured arteries. Wire-induced injury of the carotid artery in apoE-/- mice caused a rapid increase of JE/CCL2 protein in the vessel wall peaking at 24 hours after injury, whereas serum JE/CCL2 was increased solely at 6 hours and blood cell-associated levels were unaltered, as demonstrated by enzyme-linked immunosorbent assay. Immunohistochemistry revealed intense staining for JE/CCL2 in smooth muscle cells (SMCs) and in association with platelets adherent to the denuded vessel wall 24 hours after injury. In vitro, exogenous or SMC-derived JE/CCL2 binds to the platelet surface and triggers monocyte arrest on adherent platelets but not on SMCs in flow assays. Accordingly, monocyte arrest in ex vivo perfused apoE-/- carotid arteries isolated 24 hours after injury was profoundly inhibited by pretreatment with a JE/CCL2 antibody. In CCR2-/-/apoE-/- mice, neointimal plaque area was reduced by 47% compared with CCR2+/+/apoE-/- mice. Moreover, CCR2 deletion markedly decreased neointimal macrophage content while expanding SMC content. Vascular JE/CCL2 expressed by SMCs and immobilized by adherent platelets after endothelial denudation is crucial for mediating early monocyte recruitment to injured arteries in hyperlipidemic mice. This mechanism may explain reduced neointimal macrophage infiltration and lesion formation in CCR2-deficient apoE-/- mice.
Fluorine-18-labeled fluoroboronophenylalanine PET in patients with glioma. (1998)

These PET data will be of practical use for diagnosis of malignancy and direct prediction of the effectiveness of boron neutron capture therapy using 10B-BPA.
Arrayed-waveguide grating multiplexer with loop-back optical paths and its applications (1996)

We present a basic configuration of an unique integrated-optic arrayed-waveguide grating (AWG) multiplexer with loop-back optical paths and demonstrate an add-drop multiplexer (ADM), a network access terminal, and a wavelength channel selector for dense-WDM ring or bus networks, as three useful examples of its attractive applications. A key device in these components is a silica-glass based 1.55 /spl mu/m polarization-insensitive 32/spl times/32 AWG multiplexer chip with 0.8 nm channel spacing which is fabricated using planar lightwave circuit (PLC) technologies. Fine operation in their new functional components is achieved by using the AWG multiplexer module having low insertion loss of 3.9 dB and low interchannel crosstalk of less than -28 dB.
Dolutegravir (S/GSK1349572) Exhibits Significantly Slower Dissociation than Raltegravir and Elvitegravir from Wild-Type and Integrase Inhibitor-Resistant HIV-1 Integrase-DNA Complexes (2011)

The integrase inhibitor (INI) dolutegravir (DTG; S/GSK1349572) has significant activity against HIV-1 isolates with raltegravir (RAL)- and elvitegravir (ELV)-associated resistance mutations. As an initial step in characterizing the different resistance profiles of DTG, RAL, and ELV, we determined the dissociation rates of these INIs with integrase (IN)-DNA complexes containing a broad panel of IN proteins, including IN substitutions corresponding to signature RAL and ELV resistance mutations. DTG dissociates slowly from a wild-type IN-DNA complex at 37°C with an off-rate of 2.7 × 10(-6) s(-1) and a dissociative half-life (t(1/2)) of 71 h, significantly longer than the half-lives for RAL (8.8 h) and ELV (2.7 h). Prolonged binding (t(1/2), at least 5 h) was observed for DTG with IN-DNA complexes containing E92, Y143, Q148, and N155 substitutions. The addition of a second substitution to either Q148 or N155 typically resulted in an increase in the off-rate compared to that with the single substitution. For all of the IN substitutions tested, the off-rate of DTG from IN-DNA complexes was significantly slower (from 5 to 40 times slower) than the off-rate of RAL or ELV. These data are consistent with the potential for DTG to have a higher genetic barrier to resistance, provide evidence that the INI off-rate may be an important component of the mechanism of INI resistance, and suggest that the slow dissociation of DTG may contribute to its distinctive resistance profile.
The Average Structural Density of Barite Crystals of Different Habit Types (1999)

Eight different habit types of barite crystals which could be classified into 4 essentially different groups were determined by morphological analysis: E b group -barite crystals elongated in the [0 1 0] direction; E a group -barite crystals elongated in the [1 0 0] d i r e c t i o n ; T c group -barite crystals tabular on the basal pinacoid {0 0 1}; E c group -barite crystals elongated in the [001] direction.By determination and comparison of the average structural densities of different habit types of barite crystals, it was possible to establish the spans of their values from 276.1 to 495.8, and overlapping of values for E b group with E a group and T c group with E c group.The sequence of habit types, with regard to the decreasing average structural density, i.e. the priority sequence of developing of barite crystal types, was determined: E b group -E a group -T c group -E c group.
Accurate Translation of the Genetic Code Depends on tRNA Modified Nucleosides (2002)

Transfer RNA molecules translate the genetic code by recognizing cognate mRNA codons during protein synthesis. The anticodon wobble at position 34 and the nucleotide immediately 3' to the anticodon triplet at position 37 display a large diversity of modified nucleosides in the tRNAs of all organisms. We show that tRNA species translating 2-fold degenerate codons require a modified U(34) to enable recognition of their cognate codons ending in A or G but restrict reading of noncognate or near-cognate codons ending in U and C that specify a different amino acid. In particular, the nucleoside modifications 2-thiouridine at position 34 (s(2)U(34)), 5-methylaminomethyluridine at position 34 (mnm(5)U(34)), and 6-threonylcarbamoyladenosine at position 37 (t(6)A(37)) were essential for Watson-Crick (AAA) and wobble (AAG) cognate codon recognition by tRNA(UUU)(Lys) at the ribosomal aminoacyl and peptidyl sites but did not enable the recognition of the asparagine codons (AAU and AAC). We conclude that modified nucleosides evolved to modulate an anticodon domain structure necessary for many tRNA species to accurately translate the genetic code.
Phosphodiesterase 1B differentially modulates the effects of methamphetamine on locomotor activity and spatial learning through DARPP32‐dependent pathways: evidence from PDE1B‐DARPP32 double‐knockout mice (2006)

Mice lacking phosphodiesterase 1B (PDE1B) exhibit an exaggerated locomotor response to D-methamphetamine and increased in vitro phosphorylation of DARPP32 (dopamine- and cAMP-regulated phosphoprotein, M r 32 kDa) at Thr34 in striatal brain slices treated with the D1 receptor agonist, SKF81297. These results indicated a possible regulatory role for PDE1B in pathways involving DARPP32. Here, we generated PDE1B x DARPP32 double-knockout (double-KO) mice to test the role of PDE1B in DARPP32-dependent pathways in vivo. Analysis of the response to d-methamphetamine on locomotor activity showed that the hyperactivity experienced by PDE1B mutant mice was blocked in PDE1B-/- x DARPP32-/- double-KO mice, consistent with participation of PDE1B and DARPP32 in the same pathway. Further behavioral testing in the elevated zero-maze revealed that DARPP32-/- mice showed a less anxious phenotype that was nullified in double-mutant mice. In contrast, in the Morris water maze, double-KO mice showed deficits in spatial reversal learning not observed in either single mutant compared with wild-type mice. The data suggest a role for PDE1B in locomotor responses to psychostimulants through modulation of DARPP32-dependent pathways; however, this modulation does not necessarily impact other behaviors, such as anxiety or learning. Instead, the phenotype of double-KOs observed in these latter tasks may be mediated through independent pathways.
Action detection in complex scenes with spatial and temporal ambiguities (2009)

In this paper, we investigate the detection of semantic human actions in complex scenes. Unlike conventional action recognition in well-controlled environments, action detection in complex scenes suffers from cluttered backgrounds, heavy crowds, occluded bodies, and spatial-temporal boundary ambiguities caused by imperfect human detection and tracking. Conventional algorithms are likely to fail with such spatial-temporal ambiguities. In this work, the candidate regions of an action are treated as a bag of instances. Then a novel multiple-instance learning framework, named SMILE-SVM (Simulated annealing Multiple Instance LEarning Support Vector Machines), is presented for learning human action detector based on imprecise action locations. SMILE-SVM is extensively evaluated with satisfactory performances on two tasks: 1) human action detection on a public video action database with cluttered backgrounds, and 2) a real world problem of detecting whether the customers in a shopping mall show an intention to purchase the merchandise on shelf (even if they didn't buy it eventually). In addition, the complementary nature of motion and appearance features in action detection are also validated, demonstrating a boosted performance in our experiments.
Surgical Approaches to Create Murine Models of Human Wound Healing (2010)

Wound repair is a complex biologic process which becomes abnormal in numerous disease states. Although in vitro models have been important in identifying critical repair pathways in specific cell populations, in vivo models are necessary to obtain a more comprehensive and pertinent understanding of human wound healing. The laboratory mouse has long been the most common animal research tool and numerous transgenic strains and models have been developed to help researchers study the molecular pathways involved in wound repair and regeneration. This paper aims to highlight common surgical mouse models of cutaneous disease and to provide investigators with a better understanding of the benefits and limitations of these models for translational applications.
Stretchable electronics: materials, architectures and integrations (2012)

Stretchable electronics, i.e. elastic electronics that can be bent and stretched, is a new, emerging class of electronics, based on building electronic circuits or devices on stretchable substrates. The potential applications range from fully conformable, stretchable, skin sensors for robotic devices, wearable electronic devices, to flesh-like biodevices. One of the challenges in the development of stretchable electronics is to retain full functionality under high external strains in stretching. In this paper, we review a few approaches recently developed for stretchable electronics and highlight recent research efforts on multi-directional writing for stretchable, three-dimensional structures.
Lipoproteomics I: Mapping of proteins in low‐density lipoprotein using two‐dimensional gel electrophoresis and mass spectrometry (2005)

The molecular mechanisms underlying the relationship between low-density lipoprotein (LDL) and the risk of atherosclerosis are not clear. Therefore, detailed information about the protein composition of LDL may contribute to reveal its role in atherogenesis and the mechanisms that lead to coronary disease in humans. Here, we sought to map the proteins in human LDL by a proteomic approach. LDL was isolated by two-step discontinuous density-gradient ultracentrifugation and the proteins were separated with two-dimensional gel electrophoresis and identified with peptide mass fingerprinting, using matrix assisted laser desorption/ionization-time of flight-mass spectrometry and with amino acid sequencing using electrospray ionization tandem mass spectrometry. These procedures identified apo B-100, apo C-II, apo C-III (three isoforms), apo E (four isoforms), apo A-I (two isoforms), apo A-IV, apo J and apo M (three isoforms not previously described). In addition, three proteins that have not previously been identified in LDL were found: serum amyloid A-IV (two isoforms), calgranulin A, and lysozyme C. The identities of apo M, calgranulin A, and lysozyme C were confirmed by sequence information obtained after collision-induced dissociation fragmentation of peptides characteristic for these proteins. Moreover, the presence of lysozyme C was further corroborated by demonstrating enriched hydrolytic activity in LDL against Micrococcus lysodeikticus. These results indicate that in addition to the dominating apo B-100, LDL contains a number of other apolipoproteins, many of which occur in different isoforms. The demonstration, for the first time, that LDL contains calgranulin A and lysozyme C raises the possibility that LDL proteins may play hitherto unknown role(s) in immune and inflammatory reactions of the arterial wall.
Specific Docking of Apolipoprotein A-I at the Cell Surface Requires a Functional ABCA1 Transporter (2001)

The identification of defects in ABCA1 as the molecular basis of Tangier disease has highlighted its crucial role in the loading with phospholipids and cholesterol of nascent apolipoprotein particles. Indeed the expression of ABCA1 affects apolipoprotein A-I (apoA-I)-mediated removal of lipids from cell membranes, and the possible role of ABCA1 as an apoA-I surface receptor has been recently suggested. In the present study, we have investigated the role of the ABCA1 transporter as an apoA-I receptor with the analysis of a panel of transfectants expressing functional or mutant forms of ABCA1. We provide experimental evidence that the forced expression of a functional ABCA1 transporter confers surface competence for apoA-I binding. This, however, appears to be dependent on ABCA1 function. Structurally intact but ATPase-deficient forms of the transporter fail to elicit a specific cell association of the ligand. In addition the diffusion parameters of membrane-associated apoA-I indicate an interaction with membrane lipids rather than proteins. These results do not support a direct molecular interaction between ABCA1 and apoA-I, but rather suggest that the ABCA1-induced modification of the lipid distribution in the membrane, evidenced by the phosphatidylserine exofacial flopping, generates a biophysical microenvironment required for the docking of apoA-I at the cell surface.
Antibody specific for the Thr-286-autophosphorylated alpha subunit of Ca2+/calmodulin-dependent protein kinase II. (1992)

We report the production of an antibody specific for Ca2+/calmodulin-dependent protein kinase II (CaM-KII) autophosphorylated only at Thr-286 of the alpha subunit. Peptide Y-66 [sequence MHRQETVDC (Met-281 to Cys-289 of alpha subunit of CaM-KII)] was synthesized and phosphorylated by the CaM-KII endogenous to synaptic cytoskeleton (postsynaptic density-enriched fraction); the phosphorylated amino acid residue threonine corresponds to Thr-286 in the kinase alpha subunit. The phosphorylated Y-66 peptide was separated from the unphosphorylated peptide by HPLC and used as an immunogen after being coupled to hemocyanin. The antibodies that reacted with hemocyanin and unphosphorylated Y-66 peptide were adsorbed, and then IgG was purified. ELISA proved that the IgG obtained reacted specifically with phosphorylated Y-66 peptide. Immunoblot analysis showed that the antibody reacted specifically to the autophosphorylated CaM-KII both in purified and synaptic cytoskeleton-associated form. Appearance of CaM-KII subunits immunoreactive to anti-phosphorylated Y-66 antibody paralleled the generation of Ca(2+)-independent kinase activity. Immunocytochemical experiments clearly showed expression of the Thr-286- or Thr-287-autophosphorylated form of CaM-KII in cultured hippocampal cells treated with N-methyl-D-aspartate. Thus, this antibody could be extremely useful for studying the biological functions of CaM-KII.
Classifying arguments by scheme (2011)

Argumentation schemes are structures or templates for various kinds of arguments. The argumentation scheme classification system that we present in this paper intro-duces a new task in this field. To the best of our knowledge, this is the first attempt to classify arguments into argumentation schemes automatically. Given the text of an argument with premises and conclusion identified, we clas-sify it as an instance of one of five common schemes, using general features and other features specific to each scheme, including lexical, syntactic, and shallow semantic fea-tures. We achieve accuracies of 63–91 % in one-against-others classification and 80–94% in pairwise classification (baseline = 50 % in both cases). We design a pipeline framework whose ultimate goal is to reconstruct the implicit premises in an argument, and our argumentation scheme classification system is aimed to address the third component in this framework. While the first two portions of this framework can be fulfilled by work of other researchers, we propose a syntactic-based approach to the last component of this framework. The completion of the entire system
Matrix metalloproteinase degradation of elastin, type IV collagen and proteoglycan. A quantitative comparison of the activities of 95 kDa and 72 kDa gelatinases, stromelysins-1 and -2 and punctuated metalloproteinase (PUMP) (1991)

The abilities of the matrix metalloproteinases 95 kDa and 72 kDa gelatinases (type IV collagenases), stromelysins-1 and -2 and punctuated metalloproteinase (PUMP) to degrade insoluble elastin, type IV collagen films and proteoglycan have been compared. The gelatinases and PUMP were markedly more active in the degradation of elastin than were the stromelysins. PUMP and the stromelysins were more potent proteoglycan-degrading enzymes. All of the enzymes studied degraded soluble native type IV collagen, but the gelatinases were more effective at higher temperatures. These quantitative data allow an analysis of the potential relative roles of these metalloproteinases in the breakdown of the key components of connective tissue matrices.
An alternative route of infection for viruses: entry by means of the asialoglycoprotein receptor of a Sendai virus mutant lacking its attachment protein. (1985)

During the first stage of infection, the paramyxovirus Sendai virus attaches to host cells by recognizing specific receptors on the cell surface. Productive virus-cell interactions result in membrane fusion between the viral envelope and the cell surface membrane. It has recently been shown that the ganglioside GD1a and its more complex homologs GT1b and GQ1b are cell surface receptors for Sendai virus. We report in this paper that the temperature-sensitive mutant ts271 of the Enders strain of Sendai virus lacks the viral attachment protein HN and the biological activities of hemagglutination and sialidase activity associated with it when the virus is grown at 38 degrees C. This HN- virus was unable to infect or agglutinate conventional host cells that contained receptor gangliosides and were readily infected by the parental wild-type virus. The HN- virus did, however, attach to and infect Hep G2 cells, a line of hepatoma cells that retains the asialoglycoprotein receptor (ASGP-R) upon continuous culture. This receptor is a mammalian lectin that recognizes galactose- or N-acetylgalactosamine-terminated proteins. In accordance with the known properties of this receptor, infection by the HN- virus was abolished by treatment of Hep G2 cells with sialidase, by the presence of Ca2+ chelators, and by competition with N-acetylgalactosamine, asialoorosomucoid, and antibody to the receptor. F, the only glycoprotein on the HN- virus, was shown to compete with the galactose-terminated protein asialoorosomucoid for the ASGP-R. The ability of the HN- virus to cause cell-cell fusion of Hep G2 cells indicated that attachment of this virus to the ASGP-R still permitted viral entry by its usual mode--i.e., membrane fusion at the cell surface. These results open up the possibility that enveloped viruses, which contain glycosylated proteins or lipids, may make use of naturally occurring lectins in addition to their normal receptors as a means of attachment to host cells.
On-chip microband array electrochemical detector for use in capillary electrophoresis (1994)

A new electrochemical detector, designed for use with conventional capillary electrophoresis systems, is described. The sensor incorporates a platinum microband array electrode and three larger electrodes on a silicon chip. The fluid flow is facilitated over the electrodes by an etched FI glass cap which allows simple connection to separation capillaries. The device was evaluated using a series of catecholamines with the lowest detectable amount of hydroquinone being 1.4 fmol (based on three times the standard deviation (3σ) of the background noise). Comparison with ultraviolet (UV) detection, using the same separation system, indicated that electrochemical detection was more sensitive for this range of analytes. The UV detection limit of hydroquinone was 58 fmol. Despite this increased sensitivity, the separation efficiency of the electrochemical method was reduced, as expected for the off-column detection mode.