gebhart/patrepeval huggingface dataset:
Fat feeding increases size, but not number, of chylomicrons produced by small intestine (1990)

To test the regulatory effect of dietary triglyceride (TG) on rat lymphatic apolipoprotein B (apo B) transport, lymph-fistula rats were infused intraduodenally for 8 h at 3 ml/h with a lipid emulsion containing 40 mumol TG labeled with glycerol [9,10-3H(N)]triolein, 7.8 mumol egg phosphatidylcholine, and 57 mumol sodium taurocholate in phosphate-buffered saline with or without 1 mg/h Pluronic L81 (L81). L81 is known to prevent lipid transport in the intestine by inhibiting the formation of chylomicrons (CM). This action of L81 is quickly reversible by merely replacing L81 infusion by saline infusion. In the control rats (without L81 added to the infusate), the amount of apo B secreted in either whole lymph, CM, or the very-low-density lipoprotein (VLDL) fractions did not change significantly during lipid infusion compared with fasting. Compared with the fasting, the apo B output in lymph during L81 plus lipid or saline infusion in the experimental rats did not change significantly. The lymphatic apo B output data were also supported by the incorporation studies using [3H]leucine. In summary, these data demonstrate that the absorption of a physiological load of lipid into lymph does not affect the apo B synthesis in the mucosa or the secretion of apo B in lymph. Furthermore, the action of L81 is probably not by inhibiting intestinal apo B production because apo B secretion was not affected by the presence of L81. This study also demonstrates that the number of CM particles made by the small intestine remains relatively constant during fasting or active lipid uptake and transport. During active lipid absorption, instead of increasing the number of CM, the enterocytes expand the size of the CM particles. Lastly, the number and TG content of VLDL particles synthesized and secreted by the small intestine also seems to remain relatively constant during fasting and active lipid absorption.
High-Resolution NMR of an Antisense DNA·RNA Hybrid Containing Alternating Chirally Pure Rp Methylphosphonates in the DNA Backbone (1997)

A high-resolution proton NMR study has been performed on a hybrid duplex formed by a methylphosphonate (MP) oligodeoxyribonucleotide (MPO) and its target oligoribonucleotide, d(T(MP)CC(MP)-TT(MP)AG(MP)CT(MP)CC(MP)TG) x r(CAGGAGCUAAGGA), where MP corresponds to positions of methylphosphonate linkages in the pure R(p) stereoconfiguration. MP-containing analogs of DNA are reported to be effective antisense agents capable of specifically inhibiting protein synthesis with the R(p) chiral MPOs exhibiting greater affinity for the target mRNA than their S(p) counterparts. Nearly complete proton resonance assignments of the hybrid duplex have been made using two-dimensional nuclear Overhauser effect (2D NOE) spectra, at three different mixing times, and double quantum-filtered COSY (2QF-COSY) spectra. The 2QF-COSY cross-peak patterns which are resolved have been analyzed qualitatively to suggest sugar conformations. Distance restraints have been obtained from the 2D NOE spectra of the duplex in D(2)O. These interproton distance restraints were determined using a complete relaxation matrix method to improve accuracy. Specifically, a new approach termed RANDMARDI has been utilized to calculate these distance restraints, accounting for spectral noise and errors in 2D NOE peak volume integration. The calculated interproton distances and sugar puckers have been analyzed to assess the solution conformation of the hybrid. The hybrid duplex appears to have an overall solution structure which is distinct from standard B- and A-forms, but the RNA strand exhibits features of the A-form. The absence of H1'-H2' cross-peaks in the 2QF-COSY spectrum indicates a C3'-endo type of conformation for ribose sugars in the RNA strand. The deoxyriboses in the antisense DNA strand exhibit a mixed behavior with almost equal scalar coupling constant values for H1'-H2' and H1'-H2" and a strong H3'-H4' 2QF-COSY peak pattern. Variations in calculated values of interproton distances and sixth-root R factor analysis of experimental intensities indicate that the hybrid duplex may have a DNA strand with significant conformational plasticity.
Elevation of IL-6 in the allergic asthmatic airway is independent of inflammation but associates with loss of central airway function (2010)

In mild-moderate asthma, IL-6 dissociates from other proinflammatory biomarkers, but correlates with IL-13 levels. Furthermore, IL-6 may contribute to impaired lung function in allergic asthma.
Mobility modeling, location tracking, and trajectory prediction in wireless ATM networks (1998)

Wireless ATM networks require efficient mobility management to cope with frequent mobile handoff and rerouting of connections. Although much attention has been given in the literature to network architecture design to support wide-area mobility in public ATM networks, little has been done to the important issue of user mobility estimation and prediction to improve the connection reliability and bandwidth efficiency of the underlying system architecture. This paper treats the problem by developing a hierarchical user mobility model that closely represents the movement behavior of a mobile user, and that, when used with appropriate pattern matching and Kalman filtering techniques, yields an accurate location prediction algorithm, HLP, or hierarchical location prediction, which provides necessary information for advance resource reservation and advance optimal route establishment in wireless ATM networks.
Heme oxygenase-1 is a modulator of inflammation and vaso-occlusion in transgenic sickle mice (2006)

Transgenic sickle mice expressing betaS hemoglobin have activated vascular endothelium that exhibits enhanced expression of NF-kappaB and adhesion molecules that promote vascular stasis in sickle, but not in normal, mice in response to hypoxia/reoxygenation. Sickle mice hemolyze rbcs in vivo as demonstrated by increased reticulocyte counts, plasma hemoglobin and bilirubin, and reduced plasma haptoglobin. The heme content is elevated in sickle organs, which promotes vascular inflammation and heme oxygenase-1 expression. Treatment of sickle mice with hemin further increases heme oxygenase-1 expression and inhibits hypoxia/reoxygenation-induced stasis, leukocyte-endothelium interactions, and NF-kappaB, VCAM-1, and ICAM-1 expression. Heme oxygenase inhibition by tin protoporphyrin exacerbates stasis in sickle mice. Furthermore, treatment of sickle mice with the heme oxygenase enzymatic product carbon monoxide or biliverdin inhibits stasis and NF-kappaB, VCAM-1, and ICAM-1 expression. Local administration of heme oxygenase-1 adenovirus to subcutaneous skin increases heme oxygenase-1 and inhibits hypoxia/reoxygenation-induced stasis in the skin of sickle mice. Heme oxygenase-1 plays a vital role in the inhibition of vaso-occlusion in transgenic sickle mice.
VH3 family antibodies bind domain D of staphylococcal protein A. (1995)

Staphylococcal protein A (SpA) is a 45-kDa bacterial membrane protein that can interact with either Fc gamma, a constant region portion of IgG, or with the Fab portion that also mediates conventional Ag binding. In recent reports, SpA has been shown to specifically interact with Fab derived from the VH3 family and is little affected by VH CDR3, JH, or light chain usage. To identify a site on SpA responsible for VH3 Fab binding, we cloned and expressed in Escherichia coli the 61 amino acid sequence of SpA that represents domain D, and this small protein exhibited both the VH3 Fab and Fc gamma binding specificities. Surface plasmon resonance measurements demonstrated that domain D and native SpA had the strongest binding interactions with an IgM-kappa encoded by the germline configuration of the VH3 gene VH26c. In contrast, the apparent affinities for Fc gamma binding were at least fivefold weaker. A variant of domain D was also created that is devoid of the three-codon insertion that distinguishes domain D from all other domains in SpA. Although this deletion did not significantly affect the VH3 Fab-mediated SpA binding activity, it did improve the affinity of Fc gamma binding by an order of magnitude. These observations characterize a site on SpA responsible for binding interactions with B cell Ag receptors that are highly analogous to that of superantigens for T cell receptors.
Quantitative Cancer Proteomics: Stable Isotope Labeling with Amino Acids in Cell Culture (SILAC) as a Tool for Prostate Cancer Research (2004)

Microarrays have been the primary means for large-scale analyses of genes implicated in cancer progression. However, more recently a need has been recognized for investigating cancer development directly at the protein level. In this report, we have applied a comparative proteomic technique to the study of metastatic prostate cancer. This technology, termed stable isotope labeling with amino acids in cell culture (SILAC), has recently gained popularity for its ability to compare the expression levels of hundreds of proteins in a single experiment. SILAC makes use of (12)C- and (13)C-labeled amino acids added to the growth media of separately cultured cell lines, giving rise to cells containing either "light" or "heavy" proteins, respectively. Upon mixing lysates collected from these cells, proteins can be identified by tandem mass spectrometry. The incorporation of stable isotopes also allows for a quantitative comparison between the two samples. Using this method, we compared the expression levels for more than 440 proteins in the microsomal fractions of prostate cancer cells with varying metastatic potential. Of these, 60 were found elevated greater than 3-fold in the highly metastatic cells, whereas 22 were reduced by equivalent amounts. Western blotting provided further confirmation of the mass spectrometry-based quantification. Our results demonstrate the applicability of this novel approach toward the study of cancer progression using defined cell lines.
Anti-CD20 monoclonal antibody with enhanced affinity for CD16 activates NK cells at lower concentrations and more effectively than rituximab (2006)

Growing evidence indicates that the affinity of monoclonal antibodies (mAbs) for CD16 (FcgammaRIII) plays a central role in the ability of the mAb to mediate antitumor activity. We evaluated how CD16 polymorphisms, and mAb with modified affinity for target antigen and CD16, affect natural killer (NK) cell phenotype when CD20(+) malignant B cells were also present. The mAb consisted of rituximab (R), anti-CD20 with enhanced affinity for CD20 (AME-B), and anti-CD20 with enhanced affinity for both CD20 and CD16 (AME-D). Higher concentrations of mAb were needed to induce CD16 modulation, CD54 up-regulation, and antibody-dependent cellular cytotoxicity (ADCC) on NK cells from subjects with the lower affinity CD16 polymorphism. The dose of mAb needed to induce NK activation was lower with AME-D irrespective of CD16 polymorphism. At saturating mAb concentrations, peak NK activation was greater for AME-D. Similar results were found with measurement of CD16 modulation, CD54 up-regulation, and ADCC. These data demonstrate that cells coated with mAb with enhanced affinity for CD16 are more effective at activating NK cells at both low and saturating mAb concentrations irrespective of CD16 polymorphism, and they provide further evidence for the clinical development of such mAbs with the goal of improving clinical response to mAb.
An Empirical Analysis of Credit Spread Innovations (2001)

The author examines corporate bond yield spread innovations for different credit quality and maturity portfolios using option-adjusted spread data from the Salomon Brothers Yield Book for 1984–1999, and finds that credit spread volatility and the sensitivity of credit spreads to changes in economic conditions are clearly related to the credit quality and maturity of a corporate bond. These relations are largely consistent with predictions of a model of the default margin of credit spreads. Evidence is provided that a considerable portion of yield spread volatility is due to changes in the non-default margin components of the corporate bond yield spread.
Electronic Transport and Quantum Hall Effect in Bipolar Graphenep−n−pJunctions (2007)

We have developed a device fabrication process to pattern graphene into nanostructures of arbitrary shape and control their electronic properties using local electrostatic gates. Electronic transport measurements have been used to characterize locally gated bipolar graphene $p\mathrm{\text{\ensuremath{-}}}n\mathrm{\text{\ensuremath{-}}}p$ junctions. We observe a series of fractional quantum Hall conductance plateaus at high magnetic fields as the local charge density is varied in the $p$ and $n$ regions. These fractional plateaus, originating from chiral edge states equilibration at the $p\mathrm{\text{\ensuremath{-}}}n$ interfaces, exhibit sensitivity to interedge backscattering which is found to be strong for some of the plateaus and much weaker for other plateaus. We use this effect to explore the role of backscattering and estimate disorder strength in our graphene devices.
Genome Sequence and Analysis of aPropionibacterium acnesBacteriophage (2007)

Cutaneous propionibacteria are important commensals of human skin and are implicated in a wide range of opportunistic infections. Propionibacterium acnes is also associated with inflammatory acne vulgaris. Bacteriophage PA6 is the first phage of P. acnes to be sequenced and demonstrates a high degree of similarity to many mycobacteriophages both morphologically and genetically. PA6 possesses an icosahedreal head and long noncontractile tail characteristic of the Siphoviridae. The overall genome organization of PA6 resembled that of the temperate mycobacteriophages, although the genome was much smaller, 29,739 bp (48 predicted genes), compared to, for example, 50,550 bp (86 predicted genes) for the Bxb1 genome. PA6 infected only P. acnes and produced clear plaques with turbid centers, but it lacked any obvious genes for lysogeny. The host range of PA6 was restricted to P. acnes, but the phage was able to infect and lyse all P. acnes isolates tested. Sequencing of the PA6 genome makes an important contribution to the study of phage evolution and propionibacterial genetics.
A potential role for activated HER-2 in prostate cancer. (2000)

The epidermal growth factor (also known as HER or ErbB) family of receptor tyrosine kinases are important mediators of cell growth, differentiation, and survival. At present there are 10 ligands that bind directly to epidermal growth factor, HER-3, or HER-4. Although none of these ligands bind directly to HER-2, it is recruited to these receptor complexes and also becomes activated. A monoclonal antibody directed against HER-2, 2C4, inhibits the association of HER-2 with other HER family members. Ligand-activated HER-2 may also play a role in cancers, particularly those that do not overexpress HER-2 at high levels. For example, when prostate cancers progress from an androgen-dependent to an androgen-independent phenotype, epidermal growth factor pathways are frequently activated. 2C4 will inhibit the growth of both androgen-dependent and androgen-independent prostate tumors grown as xenografts in athymic mice.
Hepatic parasympathetic neural effect on glucose balance in the intact liver (1978)

Sympathetic nerves to the intact liver of the cat were selectively destroyed by injection of 6-hydroxydopamine into the portal vein 1 week prior to the experiment. Glucose output was calculated from the product of the arterial-venous glucose difference and hepatic blood flow. Hepatic blood flow was monitored by an electromagnetic flowmeter using a hepatic venous long-circuit. Stimulation of the parasympathetic nerves isolated from around the common hepatic artery produced a rapid reduction in hepatic glucose output to one-quarter of control levels by 2 min and to zero by 10 min of nerve stimulation. The data show that hepatic glucose balance is readily influenced by the hepatic parasympathetic nerves.
10-Hydroxythebaine (1999)

trans-10-Hydroxythebaine and (8S)-8-hydroxyoxycodone were identified as by-products of thebaine oxidation with hydrogen peroxide in acidic medium. Structures of isolated compounds were determined by spectral methods.
Depression and comorbidity in community-based patients with epilepsy or asthma (2004)

Depression is common in community-based epilepsy and asthma patients, and is associated with diverse impairments.
A Lentiviral cDNA Library Employing Lambda Recombination Used To Clone an Inhibitor of Human Immunodeficiency Virus Type 1-Induced Cell Death (2004)

Expression cloning technology of cDNAs is a suitable tool for identifying novel functional properties of genes. Here, we generated a lentiviral cDNA library-expressing system for human T cells based on a site-specific recombination system of phage lambda for transferring cDNA libraries with a minimum loss of its complexity. The library-transduced CD4(+) T cells were challenged with wild-type human immunodeficiency virus type 1 (HIV-1), and the cells that acquired resistance to HIV-1-induced cytopathic effect (CPE) were selected. From these cells, CD14 was isolated and proved to inhibit the entry of HIV-1 and the HIV-1-induced CPE. This cloning system allows rapid identification of genes encoding novel properties in human T cells and probably other mammalian cells.
Discovery of drug mode of action and drug repositioning from transcriptional responses (2010)

A bottleneck in drug discovery is the identification of the molecular targets of a compound (mode of action, MoA) and of its off-target effects. Previous approaches to elucidate drug MoA include analysis of chemical structures, transcriptional responses following treatment, and text mining. Methods based on transcriptional responses require the least amount of information and can be quickly applied to new compounds. Available methods are inefficient and are not able to support network pharmacology. We developed an automatic and robust approach that exploits similarity in gene expression profiles following drug treatment, across multiple cell lines and dosages, to predict similarities in drug effect and MoA. We constructed a "drug network" of 1,302 nodes (drugs) and 41,047 edges (indicating similarities between pair of drugs). We applied network theory, partitioning drugs into groups of densely interconnected nodes (i.e., communities). These communities are significantly enriched for compounds with similar MoA, or acting on the same pathway, and can be used to identify the compound-targeted biological pathways. New compounds can be integrated into the network to predict their therapeutic and off-target effects. Using this network, we correctly predicted the MoA for nine anticancer compounds, and we were able to discover an unreported effect for a well-known drug. We verified an unexpected similarity between cyclin-dependent kinase 2 inhibitors and Topoisomerase inhibitors. We discovered that Fasudil (a Rho-kinase inhibitor) might be "repositioned" as an enhancer of cellular autophagy, potentially applicable to several neurodegenerative disorders. Our approach was implemented in a tool (Mode of Action by NeTwoRk Analysis, MANTRA, http://mantra.tigem.it).
Development of Tools for the Design of Selectin Antagonists (1997)

Abstract A molecular modeling tool for the rational design of E‐selectin antagonists based on the lead structure sialyl Lewis x has been developed. The binding affinity to the receptor is considerably influenced by the entropy and consequently by the antagonist's ability to place its pharmacophores in an optimal spatial arrangement, i.e., by its preorganization for binding. The computational model assesses the preorganization of a potential selectin antagonist with the aid of Monte Carlo (jumping between wells)/stochastic dynamics [MC(JBW)/SD] simulations. The model has been validated by correlating preorganization and bioactivity of several selectin antagonists. The results suggest that only preorganized compounds are likely to bind to E‐selectin.
Rapid Effector Function in CD8+ Memory T Cells (1997)

The nature of the CD8+ T cells that underlie antiviral protective immunological memory in vivo is unclear. We have characterized peptide-specific CD8+ T lymphocytes directly ex vivo from peripheral blood in humans with past exposure to influenza virus, using single cell interferon gamma (IFN-gamma) release as a measure of effector function. In individuals in the memory state with respect to influenza virus infection, unrestimulated antigen-specific CD8+ T cells displayed IFN-gamma release within 6 h of antigen contact, identifying a population of memory CD8+ T cells that exhibit effector function without needing to divide and differentiate over several days. We have quantified circulating CD8+ effector T cells specific for six different MHC class I-restricted influenza virus epitopes. Enumeration of these CD8+ T cells gives frequencies of peptide-specific T cells that correlate with, but are in general severalfold higher than, CTL precursor frequencies derived from limiting dilution analysis, indicating that this novel population of memory CD8+ T cells has hitherto been undetected by standard means. The phenotype of these cells, which persist at a low frequency long after recovery from an acute viral infection, suggests that they play a role in protective immunological memory.
Amyloid fibril protein in type I familial amyloidotic polyneuropathy in Japanese. (1981)

Amyloid fibrils were isolated from the kidneys of two Japanese patients with type I FAP and fractionated on Sephadex G-100 gel column. The elution pattern showed three peaks. Molecular weight of the third peak protein was about 14,000, which was absent in the chromatogram obtained from the tissue of a nonamyloidotic patient. Antisera raised against whole denatured amyloid fibril components reacted with this protein, giving rise to a precipitin arc on immunoelectrophoretic analysis in the area almost corresponding to prealbumin but slightly cathodal to it. The amino acid composition of this protein was different from those of AA protein. AL protein, or normal human PreA subunit. The major subunit GAM III of amyloid fibril protein (AFj) appears immunologically related to PreA.
Bacteriophage SPP1 Chu Is an Alkaline Exonuclease in the SynExo Family of Viral Two-Component Recombinases (2003)

Many DNA viruses concatemerize their genomes as a prerequisite to packaging into capsids. Concatemerization arises from either replication or homologous recombination. Replication is already the target of many antiviral drugs, and viral recombinases are an attractive target for drug design, particularly for combination therapy with replication inhibitors, due to their important supporting role in viral growth. To dissect the molecular mechanisms of viral recombination, we and others previously identified a family of viral nucleases that comprise one component of a conserved, two-component viral recombination system. The nuclease component is related to the exonuclease of phage lambda and is common to viruses with linear double-stranded DNA genomes. To test the idea that these viruses have a common strategy for recombination and genome concatemerization, we isolated the previously uncharacterized 34.1 gene from Bacillus subtilis phage SPP1, expressed it in Escherichia coli, purified the protein, and determined its enzymatic properties. Like lambda exonuclease, Chu (the product of 34.1) forms an oligomer, is a processive alkaline exonuclease that digests linear double-stranded DNA in a Mg(2+)-dependent reaction, and shows a preference for 5'-phosphorylated DNA ends. A model for viral recombination, based on the phage lambda Red recombination system, is proposed.