gebhart/patrepeval huggingface dataset:
Synthesis of diethylenetriaminepentaacetic acid conjugated inulin and utility for cellular uptake of liposomes (1988)

The synthesis, binding of radioactive cations, liposomal encapsulation, and biodistribution of the oxidized-inulin reaction product with ethylenediamine and diethylenetriaminepentaacetic acid (4) are described. The four-step synthesis of the inulin derivative proceeded in a good overall yield of 72%. The complex of the inulin derivative with either 67Ga3+ or 111In3+ was stable in vivo and did not readily distribute into tissues, being excreted primarily in urine after intravenous administration to mice. The liposome-entrapped inulin derivative can be loaded with radioactive heavy metal cations by mobile ionophores in high radiochemical yields of 80-91%. Following the intravenous administration of the liposomal encapsulation of the indium-111-labeled inulin derivative, the entrapped compound had a biodistribution characteristic of liposomes and allowed an estimation of the extent of the intracellular uptake of liposomes. The ability of the inulin derivative to chelate many different types of metals will allow the use of this probe for studying subtle differences in tissue distribution resulting from different drug targeting or delivery protocols in the same animal by multiple labeling techniques. Moreover, the chelate-conjugated inulin permits studies of the applications of drug delivery systems in primates or human subjects by noninvasive techniques such as gamma-scintigraphic or nuclear magnetic resonance imaging methods.
Beneficial effects of exosomes secreted by cardiac-derived progenitor cells and other cell types in myocardial ischemia (2017)

When injected into acutely infarcted rodent or pig hearts, naturally secreted nanovesicles known as exosomes from cardiac-derived progenitor cells (CPCs) reduce scar size and improve cardiac function. In this regard, exosomes fully mimic the benefits of injecting their parent cells. This recognition paves the way to the development of exosome-based, cell-free treatments for heart disease that could possibly supplant cell-based therapies. Mechanisms of benefit of these vesicles are incompletely understood but cytoprotection, stimulation of angiogenesis, induction of antifibrotic cardiac fibroblasts, and modulation of M1/M2 polarization of macrophages infiltrating the infarcted region can all play important roles. Accordingly, the beneficial molecules carried by CPC-secreted exosomes have been identified only in part but cytoprotective and proangiogenic microRNAs (miRNA) and proteins have been described. Besides CPC-secreted exosomes, vesicles released from other cell types including mesenchymal stem cells (MSCs), embryonic stem cells (ESCs), and induced pluripotent stem cells (iSPCs) have also been associated with cardioprotection. This review aims to discuss recent advances in our understanding of the role of secreted vesicles in cardiac repair, with a focus on CPC-derived exosomes.
Heat Shock Protein-90 Inhibitors Increase MHC Class I-Related Chain A and B Ligand Expression on Multiple Myeloma Cells and Their Ability to Trigger NK Cell Degranulation (2009)

Modulation of the host immune system represents a promising therapeutic approach against cancer, including multiple myeloma. Recent findings indicate that the NK group 2D (NKG2D)- and DNAX accessory molecule-1 (DNAM-1)-activating receptors play a prominent role in tumor recognition and elimination by cytotoxic lymphocytes, suggesting that the levels of NKG2D and DNAM-1 ligand expression on tumor cells may be a critical factor to improve the immune response against cancer. In this study, we tested the effect of 17-allylaminogeldanamycin and radicicol, drugs targeting the heat shock protein-90 (HSP-90) chaperone protein and displaying antimyeloma activity, on the expression of NKG2D and DNAM-1 ligands in human myeloma cell lines. We demonstrate that HSP-90 inhibitors are able to up-regulate both MHC class I chain-related (MIC) A and MICB protein surface and mRNA expression in human myeloma cell lines, without any significant effect on the basal expression of the DNAM-1 ligand poliovirus receptor CD155, or induction of nectin-2 and UL16-binding proteins. Activation of the transcription factor heat shock factor-1 by HSP-90 inhibitors is essential for the up-regulation of MICA/MICB expression and knockdown of heat shock factor-1 using small hairpin RNA interference blocks this effect. Moreover, in vitro and in vivo binding of heat shock factor-1 to MICA and MICB promoters indicates that it may enhance NKG2D ligand expression at the transcriptional level. Finally, exposure to HSP-90 inhibitors renders myeloma cells more efficient to activate NK cell degranulation and a blocking Ab specific for NKG2D significantly reduces this effect. Thus, these results provide evidence that targeting NKG2D ligands expression may be an additional mechanism supporting the antimyeloma activity of HSP-90 inhibitors and suggest their possible immunotherapeutic value.
Macrophage plasticity and polarization: in vivo veritas (2012)

Diversity and plasticity are hallmarks of cells of the monocyte-macrophage lineage. In response to IFNs, Toll-like receptor engagement, or IL-4/IL-13 signaling, macrophages undergo M1 (classical) or M2 (alternative) activation, which represent extremes of a continuum in a universe of activation states. Progress has now been made in defining the signaling pathways, transcriptional networks, and epigenetic mechanisms underlying M1-M2 or M2-like polarized activation. Functional skewing of mononuclear phagocytes occurs in vivo under physiological conditions (e.g., ontogenesis and pregnancy) and in pathology (allergic and chronic inflammation, tissue repair, infection, and cancer). However, in selected preclinical and clinical conditions, coexistence of cells in different activation states and unique or mixed phenotypes have been observed, a reflection of dynamic changes and complex tissue-derived signals. The identification of mechanisms and molecules associated with macrophage plasticity and polarized activation provides a basis for macrophage-centered diagnostic and therapeutic strategies.
Phonons and phonon-related effects in prospective nanoscale semiconductor devices (2000)

The research was devoted to the theoretical investigation of lattice vibrations in low-dimensional heterostructures and bulk materials with strong polaronic coupling. The purpose of the research has been to develop the phonon theory for technologically-important materials such as nitrides of Ga and Al as well as to locate new phonon-related effects which can be utilized in artificially-created heterostructures. The electron-phonon interaction has been considered quantum mechanically.The main findings can be summarized briefly as follows: 1. Consideration of carrier-induced renormalization of acoustic phonon spectra in quantum wires revealed the possibility for the Peierls phase transition into a state with periodic lattice distortion and charge-density waves of macroscopic period in artificially-prepared structures. The phase diagram for this transition has been determined. An analytical dispersion relation for the coupled electron-phonon excitation has been derived.2. It is found that the drift of two-dimensional electrons in quantum wells can lead to efficient amplification (generation) of sub-THz coherent confined acoustic vibrations due to the Cerenkov effect when the velocity of the drifted electrons exceeds the sound velocity in the given medium. A theory has been developed to describe the confinement of acoustic modes propagating along the high-symmetry directions in cubic quantum wells.3. A theory of confinement of optical phonon modes in wurtzite quantum wells has been developed. A formalism has been derived for calculation of electron scattering rates in optically anisotropic (uniaxial) crystals and quantum wells. 4. From the comparison of the energy losses to the lattice as function of the carrier velocity obtained in frameworks of perturbative model and path-integral Thornber-Feynman approach it is found that perturbation theory can be applied for materials with intermediate polaronic coupling such a GaN and AlN. Moreover, the theoretical possibility of unique low-field runaway transport in these materials has been demonstrated.
PART 1. CURRENT CONTROVERSIES IN THE UNDERSTANDING OF NECROTIZING ENTEROCOLITIS (2003)

Necrotizing enterocolitis (NEC) has widespread implications for neonates. While mostly affecting preterm neonates, full-term neonates, especially those with congenital heart disease, are also at risk. Although the exact pathogenesis of NEC remains elusive, three major factors, a pathogenic organism, enteral feedings, and bowel compromise, coalesce in at-risk neonates to produce bowel injury. Initiation of the inflammatory cascade likely serves as a common pathway for the disorder. Clinical signs and symptoms range from mild feeding intolerance with abdominal distension to catastrophic disease with bowel perforation, peritonitis, and cardiovascular collapse. Vigilant assessment of at-risk neonates is crucial. When conservative medical management fails to halt injury, surgical intervention is often needed. Strategies to decrease the incidence and ultimately prevent NEC loom on the horizon, such as exclusive use of human breastmilk for enteral feedings and administration of probiotics.
Purification of Recombinant G Proteins from Sf9 Cells by Hexahistidine Tagging of Associated Subunits (1995)

A method is described for purification of G protein alpha and beta gamma subunits from Sf9 cells infected with recombinant baculoviruses. The subunit to be purified is coexpressed with an associated subunit bearing a hexahistidine tag. After adsorption of the oligomer to a Ni(2+)-containing column, the subunit to be purified is eluted specifically by promoting subunit dissociation with AIF4-. The alpha subunits of G12, Gq, Gz, and Gi1 and the beta 1 gamma 2 subunit complex were easily and efficiently purified by this method. Results was superior to established procedures in all cases. Purified alpha 12 was characterized for the first time. The protein has a slow rate of guanine nucleotide exchange (kon, GTP gamma S = 0.01 min-1) and a very slow kcat for hydrolysis of GTP (0.1-0.2 min-1). GTP gamma S (guanosine 5' -3-O- (thio)triphosphate) alpha 12 does not influence the activity of several adenylyl cyclases or phospholipases. Activated alpha z inhibits the activity of type I and type V adenylyl cyclases. It is a somewhat more potent inhibitor of type V adenylyl cyclase than is activated alpha i1.
Quality adaptation for congestion controlled video playback over the Internet (1999)

Streaming audio and video applications are becoming increasingly popular on the Internet, and the lack of effective congestion control in such applications is now a cause for significant concern. The problem is one of adapting the compression without requiring video-servers to re-encode the data, and fitting the resulting stream into the rapidly varying available bandwidth. At the same time, rapid fluctuations in quality will be disturbing to the users and should be avoided.In this paper we present a mechanism for using layered video in the context of unicast congestion control. This quality adaptation mechanism adds and drops layers of the video stream to perform long-term coarse-grain adaptation, while using a TCP-friendly congestion control mechanism to react to congestion on very short timescales. The mismatches between the two timescales are absorbed using buffering at the receiver. We present an efficient-scheme for the distribution of buffering among the active layers. Our scheme allows the server to trade short-term improvement for long-term smoothing of quality. We discuss the issues involved in implementing and tuning such a mechanism, and present our simulation results.
The tetraspanin CD63 enhances the internalization of the H,K-ATPase β-subunit (2003)

The tetraspanin CD63 resides in late endosomes, lysosomes, secretory vesicles, and at the plasma membrane, and it moves among these compartments. We find that CD63 is present also in tubulovesicular elements, the intracellular compartments that contain the H,K-ATPase in unstimulated gastric parietal cells. The H,K-ATPase beta-subunit and CD63 colocalize in parietal cells and form a complex that can be coprecipitated. The beta-subunit and CD63 also interact when they are coexpressed in COS-7 cells. Furthermore, expression with CD63 induces the redistribution of the beta-subunit from the cell surface to CD63+ intracellular compartments. Immunofluorescence and biochemical experiments reveal that this redistribution occurs by enhanced endocytosis of H,K-ATPase beta-subunit complexed with CD63. Coexpression of the beta-subunit with mutant CD63 polypeptides demonstrates that the enhanced internalization of the beta-subunit depends on the capacity of CD63 to interact with adaptor protein complexes 2 and 3. These data indicate that CD63 serves as an adaptor protein that links its interaction partners to the endocytic machinery of the cell and suggest a previously uncharacterized protein-trafficking role for the tetraspanins.
IL-10-induced factors belonging to the p91 family of proteins bind to IFN-gamma-responsive promoter elements. (1994)

Expression of the gene encoding the high affinity IgG receptor (Fc gamma RI) is stimulated by IFN-gamma through a promoter element designated gamma-IFN activation site (GAS). This sequence binds a transcription factor designated gamma-IFN activation factor (GAF). GAF-GAS complexes contain an IFN-regulated 91-kDa protein (p91). In mouse peritoneal macrophages, IL-4 and IL-10 influenced both basal and IFN-gamma-induced expression of Fc gamma RI in opposite ways: IL-10 was stimulatory and IL-4 repressed Fc gamma RI expression. IL-4 or IL-10 did not affect the activation of GAF by IFN-gamma, but both activated the binding of latent, receptor-activated factors (RAFTs) to the Fc gamma RI GAS. RAFTs-IL-4 and -IL-10 migrated similarly in electrophoretic mobility shift assays but could be distinguished through their specificities for different GAS sequences and their reactivity with anti-p91 antisera. These experiments also revealed two distinct RAFTs-IL-10 to be members of the p91 family of proteins. The data suggest GAS-related elements to integrate signals from IFN-gamma-, IL-4- and IL-10-activated signaling paths.
Tissue-specific regulation of IL-6 production by IL-4. Differential effects of IL-4 on nuclear factor-kappa B activity in monocytes and fibroblasts. (1993)

IL-4 inhibits production of certain proinflammatory cytokines, including IL-1 beta, TNF-alpha, and IL-6, by activated monocytes. Although monocytes are a major source of IL-6, other cell types such as fibroblasts and endothelial cells can also express this cytokine. To determine whether IL-4 inhibits IL-6 expression in non-hemopoietic cells, we investigated the effects of IL-4 on IL-6 production in both primary human fibroblasts and fibroblast lines. Rheumatoid synovial fibroblasts were evaluated in these studies because, like monocytes, they produce high levels of IL-6 when stimulated with IL-1. Although peripheral blood monocytes did not constitutively express IL-6 mRNA or protein, stimulation with IL-1 or LPS induced de novo IL-6 expression in these cells. In contrast, synovial fibroblasts displayed a significant basal level of IL-6 production, which was markedly increased after stimulation with IL-1. IL-4 suppressed IL-6 expression in monocytes, but did not inhibit IL-6 production in synovial fibroblasts. The inability of IL-4 to suppress IL-6 synthesis in rheumatoid synovial fibroblasts was not caused by a lack of IL-4R and was not unique to these cells because IL-4 also failed to inhibit IL-6 production in normal fibroblast lines derived from other tissues. Inhibition of IL-6 production by IL-4 in monocytes was associated with decreased nuclear NF-kappa B levels. However, IL-4 does not globally suppress the activity of all DNA-binding proteins because IL-4 treatment did not reduce the levels of NF-IL-6 or NF-IL-1 beta B in the same cells. Because NF-kappa B activation is required for transcription of many cytokine genes, including IL-6, the ability of IL-4 to suppress NF-kappa B activity in monocytes suggests a potential mechanism by which this molecule may inhibit the expression of multiple cytokines.
Characterization of two distinct major histocompatibility complex class I Kk-restricted T-cell epitopes within the influenza A/PR/8/34 virus hemagglutinin (1991)

Cytotoxic T-lymphocyte (CTL) clones specific for the influenza A/PR/8/34 virus hemagglutinin (HA) were isolated by priming CBA mice with a recombinant vaccinia virus expressing the HA molecule. The epitopes recognized by two of these clones, which were CD8+, Kk restricted, and HA subtype specific, were defined by using a combination of recombinant vaccinia viruses expressing HA fragments and synthetic peptides. One epitope is in the HA1 subunit at residues 259 to 266 (numbering from the initiator methionine), amino acid sequence FEANGNLI, and the other epitope is in the HA2 subunit at residues 10 to 18 (numbering from the amino terminus of the HA2 subunit), sequence IEGGWTGMI. These two peptides are good candidates for naturally processed HA epitopes presented during influenza infection, as they are the same length (eight and nine residues) as other naturally processed viral peptides presented to CTL. A comparison of the sequences of these two new epitopes with those of the three previously published Kk-restricted T-cell epitopes showed some homology among all of the epitopes, suggesting a binding motif. In particular, an isoleucine residue at the carboxy-terminal end is present in all of the epitopes. On the basis of this homology, we predicted that the Kk-restricted epitope in influenza virus nucleoprotein, previously defined as residues 50 to 63, was contained within residues 50 to 57, sequence SDYEGRLI. This shorter peptide was found to sensitize target cells at a 200-fold lower concentration than did nucleoprotein residues 50 to 63 when tested with a CTL clone, confirming the alignment of Kk-restricted epitopes.
A Cytoplasmic Protein Stimulates Normal N- ras p21 GTPase, But Does Not Affect Oncogenic Mutants (1987)

The role of guanine nucleotides in ras p21 function was determined by using the ability of p21 protein to induce maturation of Xenopus oocytes as a quantitative assay for biological activity. Two oncogenic mutant human N-ras p21 proteins, Asp12 and Val12, actively induced maturation, whereas normal Gly12 p21 was relatively inactive in this assay. Both mutant proteins were found to be associated with guanosine triphosphate (GTP) in vivo. In contrast, Gly12 p21 was predominantly guanosine diphosphate (GDP)-bound because of a dramatic stimulation of Gly12 p21-associated guanosine triphosphatase (GTPase) activity. A cytoplasmic protein was shown to be responsible for this increase in activity. This protein stimulated GTP hydrolysis by purified Gly12 p21 more than 200-fold in vitro, but had no effect on Asp12 or Val12 mutants. A similar factor could be detected in extracts from mammalian cells. It thus appears that, in Xenopus oocytes, this protein maintains normal p21 in a biologically inactive, GDP-bound state through its effect on GTPase activity. Furthermore, it appears that the major effect of position 12 mutations is to prevent this protein from stimulating p21 GTPase activity, thereby allowing these mutants to remain in the active GTP-bound state.
Change in Anatomic Distribution and Incidence of Colorectal Carcinoma Over a Period of 15 Years (2002)

The incidence of colorectal cancer has almost doubled from 1981 to 1996 in this Dutch region. The proportion of proximal colorectal cancer has increased from 25 to 37 percent. These findings add to the notion that sigmoidoscopy is not the optimal diagnostic or screening tool for colorectal cancer.
A general framework for object detection (2002)

This paper presents a general trainable framework for object detection in static images of cluttered scenes. The detection technique we develop is based on a wavelet representation of an object class derived from a statistical analysis of the class instances. By learning an object class in terms of a subset of an overcomplete dictionary of wavelet basis functions, we derive a compact representation of an object class which is used as an input to a support vector machine classifier. This representation overcomes both the problem of in-class variability and provides a low false detection rate in unconstrained environments. We demonstrate the capabilities of the technique in two domains whose inherent information content differs significantly. The first system is face detection and the second is the domain of people which, in contrast to faces, vary greatly in color, texture, and patterns. Unlike previous approaches, this system learns from examples and does not rely on any a priori (hand-crafted) models or motion-based segmentation. The paper also presents a motion-based extension to enhance the performance of the detection algorithm over video sequences. The results presented here suggest that this architecture may well be quite general.
27 Poxvirus DNA Replication (1996)

THE POXVIRAL LIFE CYCLE Poxviruses, of which vaccinia is the prototype, are complex DNA viruses that display an unusual degree of physical and genetic autonomy from the host cell. The vaccinia genome encodes most, if not all, of the functions required for three temporally regulated phases of transcription and for DNA replication (Moss 1990a,b, 1994; Traktman 1990a,b, 1991). In addition, the 192-kb genome encodes numerous proteins that interact with and modulate the inflammatory and immune responses of the host (Smith 1993). The virus also encodes two protein kinases and a protein phosphatase (Traktman et al. 1989a; Guan et al. 1991; Banham and Smith 1992; Lin et al. 1992; Rempel and Traktman 1992; Lin and Broyles 1994), suggesting that its life cycle, like that of eukaryotic cells, is regulated by dynamic networks of protein phosphorylation. Infection is initiated by the attachment of virions to an unknown receptor on the cell surface. After direct fusion of cellular and viral membranes, the inner viral core is delivered into the cytoplasmic compartment, where it remains intact for several hours. Early gene expression initiates immediately and is directed by the encapsidated transcriptional machinery. This virally encoded apparatus includes a heterodimeric transcription factor (vETF), a seven-subunit RNA polymerase, the RAP94 polymerase accessory protein, the heterodimeric capping enzyme/termination protein, and the heterodimeric poly(A) polymerase, one of whose subunits also functions as a methyltransferase during mRNA cap maturation (Moss 1990a). An encapsidated RNA helicase is also essential for transcription (Shuman 1992), and two other encapsidated NTPases are reported...