gebhart/patrepeval huggingface dataset:
Fusogenic mechanisms of enveloped-virus glycoproteins analyzed by a novel recombinant vaccinia virus-based assay quantitating cell fusion-dependent reporter gene activation (1994)

The fusogenic activities of enveloped-virus glycoproteins were analyzed by using a quantitative, sensitive, rapid, and highly versatile recombinant vaccinia virus-based assay measuring activation of a reporter gene upon fusion of two distinct cell populations. One population uniformly expressed vaccinia virus-encoded viral glycoproteins mediating specific binding and fusion activities; the other expressed the corresponding cellular receptor(s). The cytoplasm of one population also contained vaccinia virus-encoded bacteriophage T7 RNA polymerase; the cytoplasm of the other contained a transfected plasmid with the Escherichia coli lacZ gene linked to the T7 promoter. When the two populations were mixed, cell fusion resulted in activation of the LacZ gene in the cytoplasm of the fused cells; beta-galactosidase activity was assessed by colorimetric assay of detergent cell lysates or by in situ staining. We applied this approach to study the human immunodeficiency virus type 1 envelope glycoprotein (Env)-CD4 interaction. Beta-Galactosidase was detected within 1 h after cell mixing and accumulated over the next several hours. Cell fusion dependence was demonstrated by the strict requirement for both CD4 and functional Env expression and by the inhibitory effects of known fusion-blocking monoclonal antibodies and pharmacological agents. Quantitative measurements indicated much higher sensitivity compared with analysis of syncytium formation. The assay was used to probe mechanisms of the cell type specificity for Env-CD4-mediated fusion. In agreement with known restrictions, cell fusion occurred only when CD4 was expressed on a human cell type. Membrane vesicle transfer experiments indicated that CD4 initially produced in either human or nonhuman cells was functional when delivered to human cells, suggesting that the fusion deficiency with nonhuman cells was not associated with irreversible defects in CD4. We also demonstrated that the infectivity specificities of different human immunodeficiency virus type 1 isolates for peripheral blood lymphocytes versus continuous CD4+ cell lines were associated with corresponding fusion selectivities of the respective recombinant Env proteins. The assay enabled analysis of the fusogenic activity of the fusion glycoprotein/hemagglutinin-neuraminidase of the paramyxovirus simian virus 5. This system provides a powerful tool to study fusion mechanisms mediated by enveloped-virus glycoproteins, as well as to screen fusion-blocking antibodies and pharmacological agents.
Internet image archaeology (2008)

We propose a system for automatically detecting the ways in which images have been copied and edited or manipulated. We draw upon these manipulation cues to construct probable parent-child relationships between pairs of images, where the child image was derived through a series of visual manipulations on the parent image. Through the detection of these relationships across a plurality of images, we can construct a history of the image, called the visual migration map (VMM), which traces the manipulations applied to the image through past generations. We propose to apply VMMs as part of a larger internet image archaeology system (IIAS), which can process a given set of related images and surface many interesting instances of images from within the set. In particular, the image closest to the "original" photograph might be among the images with the most descendants in the VMM. Or, the images that are most deeply descended from the original may exhibit unique differences and changes in the perspective being conveyed by the author. We evaluate the system across a set of photographs crawled from the web and find that many types of image manipulations can be automatically detected and used to construct plausible VMMs. These maps can then be successfully mined to find interesting instances of images and to suppress uninteresting or redundant ones, leading to a better understanding of how images are used over different times, sources, and contexts.
UniFrac: a New Phylogenetic Method for Comparing Microbial Communities (2005)

We introduce here a new method for computing differences between microbial communities based on phylogenetic information. This method, UniFrac, measures the phylogenetic distance between sets of taxa in a phylogenetic tree as the fraction of the branch length of the tree that leads to descendants from either one environment or the other, but not both. UniFrac can be used to determine whether communities are significantly different, to compare many communities simultaneously using clustering and ordination techniques, and to measure the relative contributions of different factors, such as chemistry and geography, to similarities between samples. We demonstrate the utility of UniFrac by applying it to published 16S rRNA gene libraries from cultured isolates and environmental clones of bacteria in marine sediment, water, and ice. Our results reveal that (i) cultured isolates from ice, water, and sediment resemble each other and environmental clone sequences from sea ice, but not environmental clone sequences from sediment and water; (ii) the geographical location does not correlate strongly with bacterial community differences in ice and sediment from the Arctic and Antarctic; and (iii) bacterial communities differ between terrestrially impacted seawater (whether polar or temperate) and warm oligotrophic seawater, whereas those in individual seawater samples are not more similar to each other than to those in sediment or ice samples. These results illustrate that UniFrac provides a new way of characterizing microbial communities, using the wealth of environmental rRNA sequences, and allows quantitative insight into the factors that underlie the distribution of lineages among environments.
Controlled delivery of PDGF-BB for myocardial protection using injectable self-assembling peptide nanofibers (2005)

Endothelial cells can protect cardiomyocytes from injury, but the mechanism of this protection is incompletely described. Here we demonstrate that protection of cardiomyocytes by endothelial cells occurs through PDGF-BB signaling. PDGF-BB induced cardiomyocyte Akt phosphorylation in a time- and dose-dependent manner and prevented apoptosis via PI3K/Akt signaling. Using injectable self-assembling peptide nanofibers, which bound PDGF-BB in vitro, sustained delivery of PDGF-BB to the myocardium at the injected sites for 14 days was achieved. A blinded and randomized study in 96 rats showed that injecting nanofibers with PDGF-BB, but not nanofibers or PDGF-BB alone, decreased cardiomyocyte death and preserved systolic function after myocardial infarction. A separate blinded and randomized study in 52 rats showed that PDGF-BB delivered with nanofibers decreased infarct size after ischemia/reperfusion. PDGF-BB with nanofibers induced PDGFR-beta and Akt phosphorylation in cardiomyocytes in vivo. These data demonstrate that endothelial cells protect cardiomyocytes via PDGF-BB signaling and that this in vitro finding can be translated into an effective in vivo method of protecting myocardium after infarction. Furthermore, this study shows that injectable nanofibers allow precise and sustained delivery of proteins to the myocardium with potential therapeutic benefits.
NIPP-1, a Nuclear Inhibitory Subunit of Protein Phosphatase-1, Has RNA-binding Properties (1997)

NIPP-1 is a nuclear inhibitory subunit of protein phosphatase-1 with structural similarities to some proteins involved in RNA processing. We report here that baculovirus-expressed recombinant NIPP-1 displays RNA-binding properties, as revealed by North-Western analysis, by UV-mediated cross-linking, by RNA mobility-shift assays, and by chromatography on poly(U)-Sepharose. NIPP-1 preferentially bound to U-rich sequences, including RNA-destabilizing AUUUA motifs. NIPP-1 also associated with single-stranded DNA, but had no affinity for double-stranded DNA. The binding of NIPP-1 to RNA was blocked by antibodies directed against the COOH terminus of NIPP-1, but was not affected by prior phosphorylation of NIPP-1 with protein kinase A or casein kinase-2, which decreases the affinity of NIPP-1 for protein phosphatase-1. The catalytic subunit of protein phosphatase-1 did not bind to poly(U)-Sepharose, but it bound very tightly after complexation with NIPP-1. These data are in agreement with a function of NIPP-1 in targeting protein phosphatase-1 to RNA.
Puberty and depression: the roles of age, pubertal status and pubertal timing (1998)

The period of emergence of increased risk for depression in adolescent girls appears to be a relatively sharply demarcated developmental transition occurring in mid-puberty. Previously reported effects of the timing of puberty (which have tended to be transient) appeared less important in increase of risk for depression than pubertal status.
Age Progression/Regression by Conditional Adversarial Autoencoder (2017)

If I provide you a face image of mine (without telling you the actual age when I took the picture) and a large amount of face images that I crawled (containing labeled faces of different ages but not necessarily paired), can you show me what I would look like when I am 80 or what I was like when I was 5? The answer is probably a No. Most existing face aging works attempt to learn the transformation between age groups and thus would require the paired samples as well as the labeled query image. In this paper, we look at the problem from a generative modeling perspective such that no paired samples is required. In addition, given an unlabeled image, the generative model can directly produce the image with desired age attribute. We propose a conditional adversarial autoencoder (CAAE) that learns a face manifold, traversing on which smooth age progression and regression can be realized simultaneously. In CAAE, the face is first mapped to a latent vector through a convolutional encoder, and then the vector is projected to the face manifold conditional on age through a deconvolutional generator. The latent vector preserves personalized face features (i.e., personality) and the age condition controls progression vs. regression. Two adversarial networks are imposed on the encoder and generator, respectively, forcing to generate more photo-realistic faces. Experimental results demonstrate the appealing performance and flexibility of the proposed framework by comparing with the state-of-the-art and ground truth.
Quantum device-simulation with the density-gradient model on unstructured grids (2001)

We describe an implementation of the density-gradient device equations which is simple and works in any dimension without imposing additional requirements on the mesh compared to classical simulations. It is therefore applicable to real-world device simulation with complex geometries. We use our implementation to determine the quantum mechanical effects for a MOS-diode, a MOSFET and a double-gated SOI MOSFET. The results are compared to those obtained by a 1D-Schrodinger-Poisson solver. We also investigate a simplified variant of the density-gradient term and show that, while it can reproduce terminal characteristics, it does not give the correct density distribution inside the device.
Molecular Findings Among Patients Referred for Clinical Whole-Exome Sequencing (2014)

Whole-exome sequencing provided a potential molecular diagnosis for 25% of a large cohort of patients referred for evaluation of suspected genetic conditions, including detection of rare genetic events and new mutations contributing to disease. The yield of whole-exome sequencing may offer advantages over traditional molecular diagnostic approaches in certain patients.
Attachment of an anti-receptor antibody to non-target cells renders them susceptible to lysis by a clone of cytotoxic T lymphocytes. (1984)

The molecular basis for the dependence of antigen recognition by T cells on products of the major histocompatibility complex (MHC) is unknown, and the antigenic structures that are actually bound by T-cell receptors are ill-defined. In this study, we asked whether a monoclonal antibody (mAb) that reacts with the T-cell receptor of a clone of murine cytotoxic T lymphocytes (CTL) and not with the receptors of other CTL clones can substitute for that clone's natural ligand in specific cytolytic reactions. To answer the question, a mAb (1B2) to the receptor of a CTL clone (2C) was attached covalently to 51Cr-labeled cells that were not otherwise susceptible to lysis by clone 2C, and the cells thus modified were then tested as targets for clone 2C and other CTL clones of similar specificity. All labeled cells modified in this way, including a murine cell line that expresses no cell-surface MHC class I molecules and a human cell line, were lysed by clone 2C but not by other CTL clones. If, however, instead of attaching the mAb to the receptor of clone 2C, the cells were modified by attaching to them mAbs to other surface antigens on CTL [lymphocyte function-associated antigen (LFA-1), Thy-1.2], they were not lysed. In cytolytic titrations, the cells that had been converted by attachment of mAb 1B2 into specific targets for clone 2C were just as susceptible to lysis by that clone as the clone's natural H-2d targets (e.g., P815 cells). However, some accessory surface molecules (LFA-1, Lyt-2) that are required for clone 2C to lyse its natural H-2d targets seemed not to be required for this clone to lyse the mAb-converted target cells. By demonstrating that a variety of different cell types can be thus converted into target cells for CTL, the approach described in this study may provide opportunities to analyze further the mechanisms by which CTL destroy target cells.
Synthesis and Characterization of Network Single Ion Conductors Based on Comb-Branched Polyepoxide Ethers and Lithium Bis(allylmalonato)borate (2005)

Network single ion conductors (NSICs) based on comb-branch polyepoxide ethers and lithium bis(allylmalonato) borate have been synthesized and thoroughly characterized by means of ionic conductivity measurements, electrochemical impedance, and cycling in symmetrical Li/Li half cells, Li/V6O13 full cells in which a NSIC was used as both binder and electrolyte in the cathode electrode and as the electrolyte separator membrane, and by dynamic mechanical analysis (DMA). The substitution of the trimethylene oxide (TMO) unit into the side chains in place of ethylene oxide (EO) units increased the polymer−ion mobility (lower glass transition temperature). However, the ionic conductivity was nearly one and half orders of magnitude lower than the corresponding pure EO-based single ion conductor at the same salt concentration, which may be ascribed to the lower dielectric constant of the TMO side chains that result in a lower concentration of free conducting lithium cations. For a highly cross-linked system (EO/Li = 20), only 47 wt % plasticizing solvent (ethylene carbonate (EC)/ethyl methyl carbonate (EMC), 1/1 by wt) could be taken up, and the ionic conductivity was only increased by 1 order of magnitude over the dry polyelectrolyte, while for a less densely cross-linked system (EO/Li = 80), up to 75 wt % plasticizer could be taken up and the ionic conductivity was increased by nearly 2 orders of magnitude. A Li/Li symmetric cell that was cycled at 85 °C at a current density of 25μA cm-2 showed no concentration polarization or diffusional relaxation, which was consistent with a lithium ion transference number of 1. However, both the bulk and interfacial impedance increased after 20 cycles, which was apparently due to continued cross-linking reactions within the membrane and on the surface of the lithium electrodes. A Li/V6O13 full cell constructed using a single ion conductor gel (propylene carbonate (PC)/EMC, 1/1 in wt) was cycled at 25 °C at a current density of 25μA cm-2 and showed an initial capacity of 268 mAh g-1 of V6O13, which stabilized at around 200 mAh g-1 after the first 20 cycles. During the DMA measurements on the NSICs, it was found that besides the main glass transition (α transition) there was a distinct secondary glass transition (β transition) for NSICs having five EO units in the side chains, while this (the secondary transition) was not clearly visible in the network single ion conductors (NSICs) with shorter side chains (two, three, and four EO units). The main glass transition (α transition) was attributed to the whole network structure of the single ion conductors and secondary glass transition (β transition) appeared to be due to the complexation of lithium by the side-chain chains. Both the main glass transition and the secondary transition were found to shift to higher temperature with increasing salt concentration.
Peroxisome Senescence in Human Fibroblasts (2002)

The molecular mechanisms of peroxisome biogenesis have begun to emerge; in contrast, relatively little is known about how the organelle functions as cells age. In this report, we characterize age-related changes in peroxisomes of human cells. We show that aging compromises peroxisomal targeting signal 1 (PTS1) protein import, affecting in particular the critical antioxidant enzyme catalase. The number and appearance of peroxisomes are altered in these cells, and the organelles accumulate the PTS1-import receptor, Pex5p, on their membranes. Concomitantly, cells produce increasing amounts of the toxic metabolite hydrogen peroxide, and we present evidence that this increased load of reactive oxygen species may further reduce peroxisomal protein import and exacerbate the effects of aging.
A phase II study of adoptive immunotherapy using dendritic cells pulsed with tumor lysate in patients with hepatocellular carcinoma† (2008)

Autologous DC vaccination in patients with HCC is safe and well tolerated with evidence of antitumor efficacy assessed radiologically and serologically, with generation of antigen-specific immune responses in some cases.
Low incidence of thrombocytopenia with porcine mucosal heparin. A prospective multicenter study. (1989)

We treated 193 patients either intravenously (94) or subcutaneously (99) for at least 5 days with porcine intestinal mucosal heparin and followed them up prospectively with frequent platelet counts to determine the incidence of heparin-related thrombocytopenia and arterial thrombosis. None of the patients in the study developed severe thrombocytopenia (platelet count, less than 100 x 10(9)/L) or arterial thrombosis. Eight patients had a platelet count of 100 to 140 X 10(9)/L on one occasion, with a count of greater than 140 x 10(9)/L on the subsequent measurement. The mean (+/- SD) values of the initial and lowest platelet counts during therapy in all patients were 288 +/- 100 x 10(9)/L and 253 +/- 88 x 10(9)/L, respectively, with the lowest counts occurring on day 4.1 +/- 4.2. A least-squares line was computed for each patient to fit the day and counts; the slopes were significantly different from zero and negative in 7.8% of patients and positive in 14.5%. This multicenter study confirms the reports that the incidence of heparin-related severe thrombocytopenia and arterial thrombosis is distinctly low in patients treated with porcine-mucosal heparin.
Early IFN-gamma production and innate immunity during Listeria monocytogenes infection in the absence of NK cells. (1998)

NK cells are believed to play a mandatory role during the early phases of Listeria monocytogenes infection by producing IFN-gamma, which is required for the activation of macrophage effector functions. Mice deficient in the common cytokine receptor gamma-chain (gamma(c)-/-), which completely lack NK cells, were used to examine whether NK cells were essential for resistance to Listeria infection in vivo. Surprisingly, infected gamma(c)-/- mice showed normal innate immunity and macrophage responses against sublethal Listeria infection 2 days postinfection. At this time point, gamma(c)-/- mice showed increased blood IFN-gamma levels compared with those in noninfected controls, demonstrating an NK-independent source of IFN-gamma, which explains early resistance. Listeria-infected gamma(c)-/- x recombinase-activating gene-2-/- double-deficient mice were unable to produce IFN-gamma and were highly susceptible to L. monocytogenes. Since T cells, but not B cells, are major IFN-gamma producers, and gamma(c)-/- T cells were found to be efficient IFN-gamma producers in vitro, we conclude from these results that T cells functionally replace NK cells for the early IFN-gamma production that is necessary for activating the innate immune system following infection with L. monocytogenes. This novel observation in listeriosis underscores how the adaptive immune response can maintain and influence innate immunity.
Calmodulin kinase II–mediated sarcoplasmic reticulum Ca2+ leak promotes atrial fibrillation in mice (2009)

A trial fibrillation (AF), the most common human cardiac arrhythmia, is associated with abnormal intracellular Ca2+ handling. Diastolic Ca2+ release from the sarcoplasmic reticulum via "leaky" ryanodine receptors (RyR2s) is hypothesized to contribute to arrhythmogenesis in AF, but the molecular mechanisms are incompletely understood. Here, we have shown that mice with a genetic gain-of-function defect in Ryr2 (which we termed Ryr2R176Q/+ mice) did not exhibit spontaneous AF but that rapid atrial pacing unmasked an increased vulnerability to AF in these mice compared with wild-type mice. Rapid atrial pacing resulted in increased Ca2+/calmodulin-dependent protein kinase II (CaMKII) phosphorylation of RyR2, while both pharmacologic and genetic inhibition of CaMKII prevented AF inducibility in Ryr2R176Q/+ mice. This result suggests that AF requires both an arrhythmogenic substrate (e.g., RyR2 mutation) and enhanced CaMKII activity. Increased CaMKII phosphorylation of RyR2 was observed in atrial biopsies from mice with atrial enlargement and spontaneous AF, goats with lone AF, and patients with chronic AF. Genetic inhibition of CaMKII phosphorylation of RyR2 in Ryr2S2814A knockin mice reduced AF inducibility in a vagotonic AF model. Together, these findings suggest that increased RyR2-dependent Ca2+ leakage due to enhanced CaMKII activity is an important downstream effect of CaMKII in individuals susceptible to AF induction.
Antagonizing the α4β1 Integrin, but Not α4β7, Inhibits Leukocytic Infiltration of the Central Nervous System in Rhesus Monkey Experimental Autoimmune Encephalomyelitis (2013)

The immune system is characterized by the preferential migration of lymphocytes through specific tissues (i.e., tissue tropism). Tissue tropism is mediated, in part, by the α(4) integrins expressed by T lymphocytes. The α(4)β(1) integrin mediates migration of memory T lymphocytes into the CNS, whereas the α(4)β(7) integrin mediates migration preferentially into gastrointestinal tissue. This paradigm was established primarily from investigations in rodents; thus, the objective of this investigation was to determine if blocking the α(4)β(7) integrin exclusively would affect migration of T lymphocytes into the CNS of primates. The effects of the dual α(4)β(1) and α(4)β(7) antagonist natalizumab were compared with those of the α(4)β(7) antagonist vedolizumab on experimental autoimmune encephalomyelitis in the rhesus monkey. Animals received an initial i.v. bolus of placebo, natalizumab (30 mg/kg), or vedolizumab (30 mg/kg) before intracutaneous immunization with recombinant human myelin oligodendrocyte glycoprotein and then Ab once weekly thereafter. Natalizumab prevented CNS inflammation and demyelination significantly (p < 0.05), compared with time-matched placebo control animals, whereas vedolizumab did not inhibit these effects, despite saturating the α(4)β(7) integrin in each animal for the duration of the investigation. These results demonstrate that blocking α(4)β(7) exclusively does not inhibit immune surveillance of the CNS in primates.