gebhart/patrepeval huggingface dataset:
Flavonoids from Koelreuteria henryi and Other Sources as Protein-Tyrosine Kinase Inhibitors (1993)

The EtOH extract of Koelreuteria henryi was investigated in a search for natural products with potential protein-tryrosine kinase (PTK) inhibitory activity. The PTK inhibitory activity of the crude fractions was determined by measuring their inhibition of p56lck partially purified from bovine thymus using angiotensin I as a substrate. Analysis of those fractions that exhibited significant activity led to the isolation of kaempferol and quercetin, in addition to two kaempferol glycosides, kaempferol-O3-alpha-rhamnopyranoside [1] and kaempferol-O3-alpha-arabinopyranoside [2]. This study represents the first report on the isolation of flavonols and their PTK inhibitory activities from the genus Koelreuteria. Eight other flavonoids were also examined to study the role of the hydroxy groups on the B ring on PTK inhibitory activity.
Cell-Surface Glycosaminoglycans (1984)

The Hippo pathway was initially discovered in Drosophila melanogaster as a key regulator of tissue growth. It is an evolutionarily conserved signaling cascade regulating numerous biological processes, including cell growth and fate decision, organ size ...Read More
Engraftment of Immune-Deficient Mice with Human Hematopoietic Stem Cells (1988)

A system in which immune-deficient mice are repopulated with cells from the human myeloid lineage, and that provides an in vivo stem cell assay for human hematopoietic cells is described. Generation of the chimeric human/immune-deficient (HID) mice was dependent on the use of immune-deficient bg/nu/xid mice. Infusion of these mice with human bone marrow gave rise to increases in human macrophage progenitors during more than 5 weeks of in vivo growth, indicating the seeding, proliferation, and differentiation of human stem cells. The human identity of the progenitors was confirmed by sequence analysis and their dependence on human growth factors. The creation of HID mice lays the foundation for establishing animal models for a wide variety of human hemopathies, from leukemia to infectious disease.
Narcotic antagonistic potency of bivalent ligands which contain .beta.-naltrexamine. Evidence for simultaneous occupation of proximal recognition sites (1982)

Two-bivalent ligands (P-X-P) containing the beta-naltrexamine pharmacophore (P) and a connecting oligoethylene glycol spanner (X) were synthesized and evaluated for narcotic antagonistic activity in the guinea pig ileum (GPI) and mouse vas deferens (MVD). The bivalent ligand 2 whose spanner contains three ethylene units possessed 10-fold greater antagonistic potency than its monovalent analogue (4) in antagonizing the effects of ethylketazocine (EK) on the GPI, while no differential antagonism of morphine was observed among the compounds. In the MVD, 2 was not substantially more potent than 4 as an antagonist against [D-Ala2,D-Leu5]enkephalin (DADLE). The bivalent ligand 3, whose spanner contains six ethylene units, exhibited 15 times greater potency in antagonizing the agonist effects of DADLE on the MVD than its monovalent ligand 4. No marked increase in the ability of 3 to antagonize the effects of morphine or EK on the GPI was observed. The data indicate that mu, kappa, and delta opioid receptors exhibit different selectivity toward bivalent ligands whose spanner lengths differ. The enhanced potency associated with different receptor interactions is consistent with simultaneous occupation of proximal recognition sites. Whether such proximal recognition sites are identical or different remains to be clarified. The distance between proximal sites appears to depend on the opioid receptor subtype involved.
Mobile multimedia platforms (2002)

With the explosion in mobile telecommunications and increasing competition, mobile telephone service providers and vehicle makers are looking to develop new types of services for vehicle users. So far the services have included information about traffic conditions and support in case of breakdowns. In future digital broadcast and third generation telecommunication systems will be used to deliver interactive multimedia services into the vehicle. This paper looks at platform requirements for supporting the delivery of the new multimedia services. It considers the role of operating systems and networks in determining the flexibility and costs of the system.
Carboxyl/cholinesterases: a case study of the evolution of a successful multigene family (1999)

The evolution of organismal diversity among the Metazoa is dependent on the proliferation of genes and diversification of functions in multigene families. Here we analyse these processes for one highly successful family, the carboxyl/cholinesterases. One key to the expansion of the functional niche of this group of enzymes is associated with versatile substrate binding and catalytic machinery. Qualitatively new functions can be obtained by substitution of one or a very few amino acids. This crudely adapted new functionality is then refined rapidly by a pulse of change elsewhere in the molecule; in one case about 13% amino acid divergence occurred in 5–10 million years. Furthermore, we postulate that the versatility of the substrate binding motifs underpins the recruitment of several family members to additional noncatalytic signal transduction functions. BioEssays 21:1031–1042, 1999. © 1999 John Wiley & Sons, Inc.
A differential method of reflection coefficient extraction from FDTD simulations (1996)

A novel concept for accurate extraction of the reflection coefficient from electromagnetic simulations is proposed and implemented into the finite-difference time-domain (FDTD) method. It uses only the values of an arbitrary tangential E-field component and its derivative with respect to the longitudinal direction at one selected point, and of an arbitrary tangential H-field component and its derivative with respect to the longitudinal direction at another point. No a priori knowledge of reference impedances is needed, and the reflection coefficient is extracted from a single run of FDTD. The proposed method is directly applicable to arbitrarily shaped and inhomogeneous transmission lines.
Considerations in the development of the automatic implantable defibrillator. (1976)

A highly reliable ventricular fibrillation detector and a satisfactory electrode system for delivering defibrillating pulses to the heart play a central role in the development of an automatic implantable defibrillator suitable for clinical use. Among the four implanted electrode designs tested, the combination of an electrode placed in the superior vena cava with a conformal electrode on the apex of the heart provided satisfactory defibrillation thresholds with ease of implantation. A new sensing method is also described for which an electrogram derived from the defibrillating electrodes is used as input. A form of a density function is developed for a filtered version of the input, ventricular fibrillation being characterized by a density curve lacking a large peak occurring at a level corresponding to the baseline of the filtered signal. These ideas are being incorporated into the design of a prototype implantable defibrillator delivering pulses of 24 joules.
Pancreatic beta cells cultured from individual preneoplastic foci in a multistage tumorigenesis pathway: a potentially general technique for isolating physiologically representative cell lines. (1993)

Culturing and comparing the discrete stages of tumorigenesis provide a route to defining important components of the cancer phenotype and, in addition, present the opportunity to establish cell cultures more representative of normal cells than the ultimate malignant cancer cells. Herein we report that preneoplastic foci in one multistep tumorigenesis pathway can be cultured in vitro and show that they preserve distinctive characteristics of the normal cells from which they arose, pancreatic beta cells. In the RIP1-Tag2 line of transgenic mice, which express the simian virus 40 T antigen in insulin-producing beta cells, pancreatic islets develop into vascularized tumors in a multistage pathway. We established conditions for reproducible derivation of beta-cell lines from individual hyperplastic islets that have not yet developed into solid tumors. Most of these cell lines, designated beta HC, release insulin at physiological concentrations of glucose. In contrast to tumor-derived lines (beta TC), which are not properly regulated, the ability of the beta HC lines to respond correctly to glucose correlated with maintenance of normally depressed levels of low-Km hexokinases. Glutamic acid decarboxylase (GAD), an early autoantigen in type I diabetes, was detected in most of the beta HC lines. The relative levels of the two forms of this enzyme (GAD65 and GAD67) varied significantly between the different cell lines, suggesting independent regulation. Class I major histocompatibility complex antigens were detected on the beta HC cells, and the levels of surface major histocompatibility complex expression correlated with their capacity to serve as targets in a cytotoxic T-cell killing assay. The beta HC lines will be of value for studies of beta-cell physiology, autoantigenicity, and tumor development. This work suggests the possibility of culturing preneoplastic stages of other cancers, both to address the mechanisms of transformation and to provide a source of cells that maintain important qualities of their normal progenitors.
Effective incorporation of 2'-O-methyl-oligoribonuclectides into liposomes and enhanced cell association through modification with thiocholesterol (1992)

Cholesterol was linked to 2'-O-methyl-oligoribonucleotides (2'-OMe-RNA) via a disulfide bond by reacting the 3'-(pyridyldithio)-modified 2'-OMe-RNA with thiocholesterol in dichloromethane-methanol solution. This ligation reaction was made possible by a novel strategy in which the highly charged oligonucleotide was rendered soluble in nonaqueous solvent through conversion to a lipophilic amidinium salt. The biodegradable lipophilic modification of 2'-OMe-RNA resulted in a large increase in incorporation of such oligonucleotides into liposomes prepared by reversephase evaporation. Furthermore, association of these modified oligonucleotides with cultured TIB 73 cells was 100-fold higher than that seen with unmodified 2'-OMe-RNA in serum-free medium and about 10 to 30-fold higher in the presence of 10% calf serum. During incubation with cells, release of the internalized oligonucleotide from the thiocholesteryl moiety can be demonstrated.
Endoluminal Placement of PTFE Graft-Stent Devices in a Canine Model (1994)

Endovascular placement of stents lined with prosthetic vascular graft materials offers promise in the treatment of dissections, aneurysms, and atherosclerotic occlusive disease. This study reports the development of and initial experience with polytetraflu oroethylene (PTFE) graft-stent devices endoluminally deployed in canines. Each iliac artery in 6 heparinized dogs received a 6-mm-diameter tubular PTFE graft mounted on either an 8 mm Palmaz stent (PS) or a metallic-ringed graft attachment device (GAD). The graft-stent devices were introduced from the femoral artery through a 14 Fr delivery catheter. Positioning and balloon expansion of the graft-stent devices were aided by fluoroscopic and intravascular ultrasound (IVUS) assessment. Animals were studied acutely (n = 2) or at weeks 1, 2, 4, or 8 after placement. No interval anticoagulation was used. All 6 PTFE-PS devices remained patent. Two of 6 PTFE-GAD devices occluded (at two and four weeks, respectively) owing to initial inadequate deployment. Nonoccluding thrombus was present in an additional 2 PTFE-GAD devices (acute and at one week, respectively) and in 2 PTFE-PS devices (at one week and two weeks, respectively). Complications included groin hematomas in 2 animals (at one week and two weeks, respectively) caused by the large traumatic delivery catheter. Endoluminal placement of PTFE graft-stent devices is feasible. Accurate assessment of deployment by IVUS, reduction of delivery catheter size, and improved graft-stent design are required.
Molecular organization of the genes required for the synthesis of type 1 capsular polysaccharide of Streptococcus pneumoniae: formation of binary encapsulated pneumococci and identification of cryptic dTDP‐rhamnose biosynthesis genes (1997)

We report here the molecular organization of the capsular locus (cap1) of the type 1 pneumococcus. This locus is located between dexB and aliA and flanked by IS1167 insertion elements. Sequence analysis showed that the cluster contains 11 genes (cap1A to cap1K), which are apparently arranged as a single transcriptional unit. The presence of a functional promoter (cap1p) located upstream of cap1A has been demonstrated and the transcription start point was mapped by primer-extension analysis. A 14.3 kb fragment containing the genes cap1ABCDEFGHIJK and including cap1p was sufficient to allow the synthesis of a type 1 capsule in Streptococcus pneumoniae. An internal deletion of cap1E leads to an unencapsulated phenotype demonstrating that this gene is essential for capsular production. The cap1K gene has been expressed in Escherichia coli resulting in UDP-glucose dehydrogenase (UDP-GlcDH) activity. Moreover, this gene was able to restore the synthesis of type 3 capsule when cloned into a plasmid and introduced by transformation into S. pneumoniae cap3A mutants deficient in UDP-GlcDH. In marked contrast with what was previously thought, recombination between cap1K and cap3A does occur. We provide data on the molecular mechanism that leads to the formation of binary encapsulated pneumococcal cells, i.e. strains that simultaneously produce type 1 and type 3 capsules. Downstream of cap1K, one truncated and three complete open reading frames homologous to those involved in the biosynthesis of dTDP-rhamnose, a monosaccharide that does not participate in the formation of type 1 polysaccharide, have been identified in all the clinical strains of type 1 pneumococcus tested. Our results provide new insights into the generation of capsule diversity in pneumococci.
Is plasminogen activator inhibitor-1 the molecular switch that governs urokinase receptor-mediated cell adhesion and release? (1996)

Induction of the urokinase type plasminogen activator receptor (uPAR) promotes cell adhesion through its interaction with vitronectin (VN) in the extracellular matrix, and facilitates cell migration and invasion by localizing uPA to the cell surface. We provide evidence that this balance between cell adhesion and cell detachment is governed by PA inhibitor-1 (PAI-1). First, we demonstrate that uPAR and PAI-1 bind to the same site in VN (i.e., the amino-terminal somatomedin B domain; SMB), and that PAI-1 competes with uPAR for binding to SMB. Domain swapping and mutagenesis studies indicate that the uPAR-binding sequence is located within the central region of the SMB domain, a region previously shown to contain the PAI-1-binding motif. Second, we show that PAI-1 dissociates bound VN from uPAR and detaches U937 cells from their VN substratum. This PAI-1 mediated release of cells from VN appears to occur independently of its ability to function as a protease inhibitor, and may help to explain why high PAI-1 levels indicate a poor prognosis for many cancers. Finally, we show that uPA can rapidly reverse this effect of PAI-1. Taken together, these results suggest a dynamic regulatory role for PAI-1 and uPA in uPAR-mediated cell adhesion and release.
Non-CD28 Costimulatory Molecules Present in T Cell Rafts Induce T Cell Costimulation by Enhancing the Association of TCR with Rafts (2000)

While CD28 functions as the major T cell costimulatory receptor, a number of other T cell molecules have also been described to induce T cell costimulation. Here, we investigated the mechanisms by which costimulatory molecules other than CD28 contribute to T cell activation. Non-CD28 costimulatory molecules such as CD5, CD9, CD2, and CD44 were present in the detergent-insoluble glycolipid-enriched (DIG) fraction/raft of the T cell surface, which is rich in TCR signaling molecules and generates a TCR signal upon recruitment of the TCR complex. Compared with CD3 ligation, coligation of CD3 and CD5 as an example of DIG-resident costimulatory molecules led to an enhanced association of CD3 and DIG. Such a DIG redistribution markedly up-regulated TCR signaling as observed by ZAP-70/LAT activation and Ca2+ influx. Disruption of DIG structure using an agent capable of altering cholesterol organization potently diminished Ca2+ mobilization induced by the coligation of CD3 and CD5. This was associated with the inhibition of the redistribution of DIG although the association of CD3 and CD5 was not affected. Thus, the DIG-resident costimulatory molecules exert their costimulatory effects by contributing to an enhanced association of TCR/CD3 and DIG.
Immunotherapy, Vascular Pathology, and Microhemorrhages in Transgenic Mice (2009)

Alzheimer's disease (AD) is a progressive, neurodegenerative disorder that results in severe cognitive decline. Amyloid plaques are a principal pathology found in AD and are composed of aggregated amyloid-beta (Abeta) peptides. According to the amyloid hypothesis, Abeta peptides initiate the other pathologies characteristic for AD including cognitive deficits. Immunotherapy against Abeta is a potential therapeutic for the treatment of humans with AD. While anti-Abeta immunotherapy has been shown to reduce amyloid burden in both mouse models and in humans, immunotherapy also exacerbates vascular pathologies. Cerebral amyloid angiopathy (CAA), that is, the accumulation of amyloid in the cerebrovasculature, is increased with immunotherapy in humans with AD and in mouse models of amyloid deposition. CAA persists in the brains of clinical trial patients that show removal of parenchymal amyloid. Mouse model studies also show that immunotherapy results in multiple small bleeds in the brain, termed microhemorrhages. The neurovascular unit is a term used to describe the cerebrovasculature and its associated cells-astrocytes, neurons, pericytes and microglia. CAA affects brain perfusion and there is now evidence that the neurovascular unit is affected in AD when CAA is present. Understanding the type of damage to the neurovascular unit caused by CAA in AD and the underlying cause of microhemorrhage after immunotherapy is essential to the success of therapeutic vaccines as a treatment for AD.
Tumor necrosis factor-α in a porcine bronchial model of obliterative bronchiolitis1 (2003)

These results indicate that TNF-alpha promotes the development of OB, and inhibition of TNF-alpha may prove beneficial in a clinical setting.
Specific and nontoxic silencing in mammalian cells with expressed long dsRNAs (2006)

A number of groups have developed libraries of siRNAs to identify genes through functional genomics. While these studies have validated the approach of making functional RNAi libraries to understand fundamental cellular mechanisms, they require information and knowledge of existing sequences since the RNAi sequences are generated synthetically. An alternative strategy would be to create an RNAi library from cDNA. Unfortunately, the complexity of such a library of siRNAs would make screening difficult. To reduce the complexity, longer dsRNAs could be used; however, concerns of induction of the interferon response and off-target effects of long dsRNAs have prevented their use. As a first step in creating such libraries, long dsRNA was expressed in mammalian cells. The 250 nt dsRNAs were capable of efficiently silencing a luciferase reporter gene that was stably transfected in MDA-MB-231 cells without inducing the interferon response or off-target effects any more than reported for siRNAs. In addition, a long dsRNA expressed in the same cell line was capable of silencing endogenous c-met expression and inhibited cell migration, whereas the dsRNA against luciferase had no effect on c-met or cell migration. The studies suggest that large dsRNA libraries are feasible and that functional selection of genes will be possible.
Enhancing DNA Vaccine Potency by Combining a Strategy to Prolong Dendritic Cell Life with Intracellular Targeting Strategies (2003)

We have recently shown that intradermal coadministration of DNA encoding Ag with DNA encoding inhibitors of apoptosis, including Bcl-x(L), prolongs dendritic cell (DC) life and thereby enhances the potency of DNA vaccines in vivo. We have also demonstrated that DNA vaccines targeting Ag to subcellular compartments, using proteins such as Mycobacterium tuberculosis heat shock protein 70, calreticulin, or the sorting signal of the lysosome-associated membrane protein type 1 (LAMP-1), enhanced DNA vaccine potency. In this study, we reasoned that the combination of a strategy to prolong DC life with intracellular targeting strategies might produce a more effective DNA vaccine against human papillomavirus E7. We showed that coadministration of DNA encoding Bcl-x(L) with DNA encoding E7/heat shock protein 70, calreticulin/E7, or Sig/E7/LAMP-1 resulted in further enhancement of the E7-specific CD8(+) T cell response for all three constructs. Of these strategies, mice vaccinated with Sig/E7/LAMP-1 DNA mixed with Bcl-x(L) DNA showed the greatest increase in E7-specific CD8(+) T cells ( approximately 13-fold increase). This combination of strategies resulted in increased CD8(+) T cell functional avidity, an increased E7-specific CD4(+) Th1 cell response, enhanced tumor treatment ability, and stronger long-term tumor protection when compared with mice vaccinated without Bcl-x(L) DNA. Therefore, DNA vaccines that combine strategies to enhance intracellular Ag processing and prolong DC life have potential clinical implications for control of viral infection and neoplasia.
Video-Assisted Film Editing System (1982)

The past few years have seen enormous progress in videotape editing. Computerized editing systems largely have eliminated the manual tasks and have made frame-accurate edits fast and easy. Film editing, on the other hand, has continued to be a manual process, involving a great deal of physical handling of the medium. There are substantial benefits to the producers of motion pictures if they take advantage of electronic editing techniques. Essentially, this means that while the original production medium and the final product are film, the editing medium itself should be videotape. Such a technique reduces the cutting and splicing of film that is necessary, limiting these operations to the final conforming assembly.
Expression of MD Infectious Bursal Disease Viral Proteins in Baculovirus (1997)

Genomic segment A of the variant infectious bursal disease virus (IBDV) strain MD was amplified by reverse transcriptase/polymerase chain reaction and further characterized by baculovirus expression. Three different baculovirus clones were constructed containing the genes encoding VP2, VP2/VP4, and the complete polyprotein cloned into the baculovirus transfer vector pVL1392. Baculovirus recombinants were identified by dot blot hybridization and were plaque purified three times. Baculovirus expression of the recombinants produced IBDV-specific proteins that were comparable in molecular size to native MD IBDV viral proteins VPX (48 kD), VP2 (45 kD), VP3 (32 kD), and VP4 (28 kD) as determined by sodium dodecyl sulfare-polyacrylamide gel electrophoresis and western immunoblot analysis. All three recombinants produced a 48-kD protein that possibly represents VPX, the precursor product of VP2. In addition to the 48-kD protein, the VP2/VP4 recombinant produced an IBDV-specific protein corresponding to the 28-kD VP4. The baculovirus-expressed polyprotein gene produced, in addition to the 48-kD protein, a 32-kD (VP3) IBDV-specific protein and a 29-kD protein that migrated slightly slower than MD VP4. The baculovirus-expressed proteins were used as antigens in an indirect enzyme-linked immunosorbent assay (ELISA). The ELISAs detected antibodies against the variant IBDV strains MD, GLS, and IN and the classic IBDV strains SAL and STC but did not detect antibodies against the variant Del-A and classic IBDV strain BVM or the serotype 2 IBDV strain OH.