gebhart/patrepeval huggingface dataset:
In vivo bronchodilator activity of vasoactive intestinal peptide in the cat. (1983)

Vasoactive intestinal peptide (VIP) is an octacosapeptide that occurs widely in the animal kingdom, is distributed in many organs and tissues, and has a broad range of biologic actions. We evaluated the ability of VIP to produce bronchodilation in anesthetized, mechanically ventilated, atropinized, closed chest cats. Boluses of VIP injected intravenously (0.1 to 10 micrograms X kg-1) reversed in a dose-dependent manner the increase in lung resistance (RL) and the decrease in dynamic lung compliance (Cdyn) induced by an intravenously administered infusion of 5-hydroxytryptamine (5HT) (5 to 30 micrograms X kg-1 X min-1). Distribution of bronchodilator activity was assessed by using RL as an index of central airways caliber and dynamic elastance (Edyn; the inverse of Cdyn) as an index of tone in peripheral airways and lung parenchyma. Although all levels of the tracheobronchial tree responded to VIP, the predominant site of action appeared to be in central airways. A similar distribution and magnitude of relaxant effects were observed after the intravenous administration of prostaglandin E2 (PGE2) (0.1 to 10 micrograms X kg-1). Prostaglandin E2 also was effective in reversing 5HT-induced bronchoconstriction when given by ultrasonic nebulization, whereas VIP was not. Bronchodilation mediated by VIP persisted after pretreatment with indomethacin or propranolol. We conclude that VIP is a potent relaxant of feline airways smooth muscle in vivo and that this effect of the peptide occurs independent of prostaglandin production or beta adrenergic receptor activation.
Eukaryotic DNA methylation as an evolutionary device (1999)

DNA methylation is catalyzed by a family of conserved DNA methyltransferases and is widespread among protists, plants, fungi and animals. It is however absent in some species and its genomic distribution varies among organisms. Sequence comparisons suggest that known and putative eukaryotic DNA methyltransferases fall into at least five structurally distinct subfamilies. Furthermore, it is now clear that DNA methylation can be involved in several functions, some of which may coexist within the same organism. It can inhibit transcription initiation, arrest transcript elongation, act as an imprinting signal, and suppress homologous recombination. On the basis of these observations, we argue that DNA methylation has been conserved during evolution because it provides unique possibilities for setting up functions of various types.
Oil-Based Foam and Proper Underbalanced-Drilling Practices Improve Drilling Efficiency in a Deep Gulf Coast Well (2008)

Abstract A recyclable oil-based foam drilling fluid (OBFDF) system has been developed to expand the benefits of controlled pressure drilling with foam onto water sensitive formations. This paper describes chemical development and presents drilling results for a Gulf Coast well drilled with the oil-based foam system. Not only did results confirm the ability of the foam system to control fluid loss and preserve formation permeability, but also, show the advantages of drilling with foam. Furthermore, a bit trip was saved drilling the reservoir in a single bit run, with a high rate of penetration and reduced gas inflow while drilling. The OBFDF is versatile, stable at high temperature (up to 450°F), compatible with H2S scavengers and reusable. Foam properties were successfully adjusted in presence of gas and condensate inflow. Still, the flexibility of foaming, defoaming and refoaming allowed surface separation and fluids reuse. Therefore, recycling liquid make up hydrocarbon reduced fluids and chemical usage with the associated cost reduction. Onsite modeling showed the controlled pressure contractor modeling software used for water-based foams can be adjusted to properly predict drilling parameters with oil-based foams.
Three 4‐coumarate:coenzyme A ligases in Arabidopsis thaliana represent two evolutionarily divergent classes in angiosperms (1999)

The enzyme 4-coumarate:CoA ligase (4CL) plays a key role in channelling carbon flow into diverse branch pathways of phenylpropanoid metabolism which serve important functions in plant growth and adaptation to environmental perturbations. Here we report on the cloning of the 4CL gene family from Arabidopsis thaliana and demonstrate that its three members, At4CL1, At4CL2 and At4CL3, encode isozymes with distinct substrate preference and specificities. Expression studies revealed a differential behaviour of the three genes in various plant organs and upon external stimuli such as wounding and UV irradiation or upon challenge with the fungus, Peronospora parasitica. Phylogenetic comparisons indicate that, in angiosperms, 4CL can be classified into two major clusters, class I and class II, with the At4CL1 and At4CL2 isoforms belonging to class I and At4CL3 to class II. Based on their enzymatic properties, expression characteristics and evolutionary relationships, At4CL3 is likely to participate in the biosynthetic pathway leading to flavonoids whereas At4CL1 and At4CL2 are probably involved in lignin formation and in the production of additional phenolic compounds other than flavonoids.
Prolonged Regional Nerve Blockade (1996)

Prolonged percutaneous blockade of peripheral nerves is feasible. The recovery from blockade is complete, and plasma bupivacaine levels are far below the range associated with systemic toxicity. The mechanisms underlying the dexamethasone block-prolonging effect are under investigation.
Performance evaluation of selective cell discard schemes in ATM networks (2002)

In transport-layer protocols such as TCP over ATM networks, a packet is discarded when one or more cells are lost in that packet, and the destination node then requires its source to retransmit the corrupted packet. Therefore, once one of the cells constituting a packet is lost, the subsequent cells of the corrupted packet waste network resources. Thus, discarding those cells will enable us to efficiently utilize the network resources and improve the packet loss probability. We focus on tail dropping (TD) and early packet discard (EPD) as selective cell discard schemes which force the switches to discard some of the arriving cells instead of relaying them. We exactly analyze the packet loss probability in a system applying these schemes. Their advantage and limits are then discussed based on numerical results derived through the analysis.
Attenuating pregnane X receptor (PXR) activation: A molecular modelling approach (2006)

Recent studies have demonstrated that the pregnane X receptor (PXR) is a key regulator of cytochromes P450 3A (e.g. CYP3A4 in human) gene expression. As a result, activation of PXR may lead to CYP3A4 protein over-expression. Because induction of CYP3A4 could result in clinically important drug drug interactions, there has been a great interest in reducing the possibility of PXR activation by drug candidates in drug-discovery programmes. In order to provide structural insight for attenuating drug candidate-mediated PXR activation, we used a docking approach to study the structure activity relationship for PXR activators. Based on our docking models, it is proposed that introducing polar groups to the end of an activator should reduce its human PXR (hPXR) activity via destabilizing interactions in the hydrophobic areas of the PXR ligand-binding pocket. A number of analogues that incorporate these structural features then were designed and synthesized, and they exhibited significantly lower hPXR activation in a transactivation assay and decreased CYP3A4 induction in a human hepatocytes-based assay. In addition, an example in which attenuating hPXR activation was achieved by sterically destabilizing the helices 11 and 12 of the receptor is presented.
Identification of Outliers in Hyperspectral Raman Image Data by Nearest Neighbor Comparison (2002)

A new algorithm for removal of cosmic spikes from hyperspectral Raman image data sets is presented. Spectra in a 3 × 3 pixel neighborhood are used to identify outlier-contaminated data points in the central pixel of that neighborhood. A preliminary despiking of the neighboring spectra is performed by median filtering. Correlations between the central pixel spectrum and its despiked neighbors are calculated, and the most highly correlated spectrum is used to identify outliers. Spike-contaminated data are replaced using results of polynomial interpolation. Because the neighborhood contains spectra obtained in three different frames, even large multi-pixel spikes are identified. Spatial, spectral, and temporal variation in signal is used to accurately identify outliers without the acquisition of any spectra other than those needed to generate the image itself. Sharp boundaries between regions of high chemical contrast do not interfere with outlier identification.
Endogenously synthesized peptide with an endoplasmic reticulum signal sequence sensitizes antigen processing mutant cells to class I-restricted cell-mediated lysis. (1991)

The HLA-A2-positive human mutant cell line T2 is not lysed by influenza virus-specific HLA-A2-restricted cytotoxic lymphocytes after virus infection. However, lysis does occur when cells are incubated with the antigenic influenza matrix protein-derived peptide M57-68. To examine the nature of this defect, T2 cells were transfected with two different plasmids. One plasmid encoded the peptide M57-68, and the other encoded the same peptide preceded by an endoplasmic reticulum translocation signal sequence. Mutant T2 cells expressing the M57-68 peptide without the signal sequence were not susceptible to lysis by M57-68-specific HLA-A2-restricted cytotoxic T lymphocytes, whereas T2 cells expressing the M57-68 peptide plus signal sequence were lysed effectively. Lysis of parental T1 cells with either plasmid was equally effective. These results suggest that the T2 mutant cells are defective in the transport of antigenic peptides from the cytosol into the secretory pathway.
Correlation between the amino acid position of arginine in VH-CDR3 and specificity for native DNA among autoimmune antibodies (1996)

Autoimmunity to DNA in mouse models for the systemic autoimmune disease systemic lupus erythematosus (SLE) has all of the characteristics of an Ag-driven secondary immune response to DNA. Since the pathogenesis of anti-DNA Ab in SLE is correlated to Ab specificity for native DNA (dsDNA), understanding how such specificity is generated is important. As with immune A responses to most Ags, autoimmune Ab responses to DNA are dependent upon the clonal selection of B cells expressing particular H and L chain V-region structures. The VH structures of most autoimmune anti-DNA Abs include at least one arginine in VH-CDR3; moreover, previous results led us to propose that anti-DNA Ab specificity for dsDNA may be dependent upon the relative position of arginines in VH-CDR3. The present results demonstrate a strong correlation between specificity for dsDNA and arginine position in VH-CDR3, for Abs with V, encoded by VH genes from the VH7183, VHQ52, and VHS107 families but not from the VH558 family. Specificity for dsDNA was not only correlated to the presence of VH-CDR3 arginines but also to the relative position of the arginines in VH-CDR3. The majority of the VH-CDR3 arginines appeared to have been encoded by sequences generated during V-D-J recombination. These results are not only important for understanding how A specificity for dsDNA is generated but also how somatically derived structures generated during V-D-J recombination may influence clonotype selection of an immune response within an individual mouse.
Bacterial lipopolysaccharide induces endothelial cells to synthesize a degranulating factor for neutrophils (1998)

Enzymes and other factors secreted by degranulating neutrophils (polymorphonuclear leukocytes, PMNs) mediate endothelial injury, thrombosis, and vascular remodeling. In bacteremia and sepsis syndrome and their consequent complications (including acute respiratory distress syndrome and systemic ischemia-reperfusion resulting from septic shock), neutrophil degranulation is an important mechanism of injury. In related studies, we found that human endothelial cells regulate neutrophil degranulation and that inflammatory cytokines induce synthesis of degranulating factors by human endothelial cells. Here we show that lipopolysaccharides (LPS) from gram-negative bacteria were the most potent agonists for release of degranulating activity by endothelial cells when compared to several cytokines and stimulatory factors. LPS also induced the release of degranulating signals for PMNs from a human endothelial cell line, EA.hy 926. Interleukin 8 (IL-8) is synthesized by endothelial and EA.hy 926 cells in response to LPS and induces neutrophil degranulation. However, complementary strategies using receptor desensitization, translation of messenger RNA by Xenopus laevis oocytes, and purification and analysis of factors from conditioned supernatants demonstrated that degranulating factors distinct from IL8 are generated in response to LPS. The characteristics of a partially purified degranulating factor isolated from conditioned supernatants distinguished it from known chemokines and other factors that induce PMN degranulation and are generated by endothelial cells in response to LPS. Thus, cultured human endothelial cells and endothelial cell lines synthesize several unique signaling molecules that can trigger neutrophil granular secretion. If produced in vivo in response to LPS or other pathologic agonists, these degranulating signals may activate PMNs in combination or in sequence, initiating or propagating vascular damage.
Synthesis and Evaluation of Hydrophilic Linkers for Antibody–Maytansinoid Conjugates (2011)

The synthesis and biological evaluation of hydrophilic heterobifunctional cross-linkers for conjugation of antibodies with highly cytotoxic agents are described. These linkers contain either a negatively charged sulfonate group or a hydrophilic, noncharged PEG group in addition to an amine-reactive N-hydroxysuccinimide (NHS) ester and sulfhydryl reactive termini. These hydrophilic linkers enable conjugation of hydrophobic organic molecule drugs, such as a maytansinoid, at a higher drug/antibody ratio (DAR) than hydrophobic SPDB and SMCC linkers used earlier without triggering aggregation or loss of affinity of the resulting conjugate. Antibody-maytansinoid conjugates (AMCs) bearing these sulfonate- or PEG-containing hydrophilic linkers were, depending on the nature of the targeted cells, equally to more cytotoxic to antigen-positive cells and equally to less cytotoxic to antigen-negative cells than conjugates made with SPDB or SMCC linkers and thus typically displayed a wider selectivity window, particularly against multidrug resistant (MDR) cancer cell lines in vitro and tumor xenograft models in vivo.
Porcine Epidemic Diarrhea Virus RNA Present in Commercial Spray-Dried Porcine Plasma Is Not Infectious to Naïve Pigs (2014)

Porcine epidemic diarrhea virus emerged in North America in April 2013 and has since been identified in 30 U.S. States, Canada and Mexico. The rapid spread of PEDV has raised concerns about the role of feed and particularly pork-by-product components such as spray-dried porcine plasma (SDPP) in PEDV transmission. The aim of this study was to determine the infectivity of PEDV RNA present in commercial SDPP. Specifically, 40 3-week-old PEDV naïve pigs were randomly assigned to one of five treatment groups. At day post inoculation (dpi) 0, NEG-CONTROL pigs were sham-inoculated, PEDV-CONTROL pigs received cell culture propagated PEDV, and SDPP-CONTROL pigs were switched to a diet with 5% SDPP containing 5.1±0.1 log10 PEDV RNA copies/g. To evaluate a potential positive effect of anti-PEDV antibodies in SDPP on PEDV challenge, four days prior to PEDV challenge the pigs in the SDPP-PEDV group were switched to and remained on a 5% SDPP diet through dpi 28. Another group, EGG-PEDV, was orally administered a commercial egg-derived liquid PEDV globulin product from dpi -4 through 6. All PEDV-CONTROL pigs began shedding PEDV in feces by dpi 3 and seroconverted between dpi 7 and 14, whereas pigs in NEG-CONTROL and SDPP-CONTROL groups remained PEDV RNA negative and did not seroconvert to PEDV for the study duration. This indicates no evidence of infectivity of the PEDV RNA in the SDPP lot utilized. Furthermore, under the study conditions SDPP or egg-derived liquid PEDV globulin addition did not significantly alter PEDV-shedding or overall disease course after experimental challenge.
Automatic Combination of Microfluidic Nanoliter-Scale Droplet Array with High-Speed Capillary Electrophoresis (2016)

In this paper, we developed a novel approach for interfacing a microfluidic two-dimensional droplet array to a high-speed capillary electrophoresis (HSCE) system. Picoliter-scale sample injection (ca. 200 pL) from a nanoliter-scale droplet array covered by nonvolatile oil was automatically achieved using the spontaneous injection mode, without the interference from the cover oil and the need of special droplet extraction interface as in previously reported systems. The system was applied in consecutive separations of 25 different samples of amino acids with a whole separation time less than 15 min, as well as on-line monitoring of in-droplet derivatizing reaction of amino acids by fluorescein isothiocyanate (FITC) over 3 hours. High separation speed (up to 100 samples per hour) and high separation efficiency (up to 9.22 × 10(5) N/m) were achieved.
Prognostic Factors Following Curative Resection for Pancreatic Adenocarcinoma (2003)

Although biologic characteristics remain important predictors of survival for patients with resected pancreatic cancer, the most powerful determinant is postoperative adjuvant chemoradiation therapy. An interesting finding that warrants further investigation is the effect of socioeconomic status on both the likelihood of receiving adjuvant treatment and subsequent survival, indicating a possible relationship between the quality of care delivered and outcomes.
Specific role for acyl CoA (2009)

Our findings identify a specific role for hepatic DGAT1 in esterification of exogenous fatty acids and indicate that DGAT1 contributes to hepatic steatosis induced by this mechanism.
A Lectin HPLC Method to Enrich Selectively-glycosylated Peptides from Complex Biological Samples (2009)

Glycans are an important class of post-translational modifications. Typically found on secreted and extracellular molecules, glycan structures signal the internal status of the cell. Glycans on tumor cells tend to have abundant sialic acid and fucose moieties. We propose that these cancer-associated glycan variants be exploited for biomarker development aimed at diagnosing early-stage disease. Accordingly, we developed a mass spectrometry-based workflow that incorporates chromatography on affinity matrices formed from lectins, proteins that bind specific glycan structures. The lectins Sambucus nigra (SNA) and Aleuria aurantia (AAL), which bind sialic acid and fucose, respectively, were covalently coupled to POROS beads (Applied Biosystems) and packed into PEEK columns for high pressure liquid chromatography (HPLC). Briefly, plasma was depleted of the fourteen most abundant proteins using a multiple affinity removal system (MARS-14; Agilent). Depleted plasma was trypsin-digested and separated into flow-through and bound fractions by SNA or AAL HPLC. The fractions were treated with PNGaseF to remove N-linked glycans, and analyzed by LC-MS/MS on a QStar Elite. Data were analyzed using Mascot software. The experimental design included positive controls-fucosylated and sialylated human lactoferrin glycopeptides-and negative controls-high mannose glycopeptides from Saccharomyces cerevisiae-that were used to monitor the specificity of lectin capture. Key features of this workflow include the reproducibility derived from the HPLC format, the positive identification of the captured and PNGaseF-treated glycopeptides from their deamidated Asn-Xxx-Ser/Thr motifs, and quality assessment using glycoprotein standards. Protocol optimization also included determining the appropriate ratio of starting material to column capacity, identifying the most efficient capture and elution buffers, and monitoring the PNGaseF-treatment to ensure full deglycosylation. Future directions include using this workflow to perform mass spectrometry-based discovery experiments on plasma from breast cancer patients and control individuals.
Antibacterial Activities of Short Designer Peptides: a Link between Propensity for Nanostructuring and Capacity for Membrane Destabilization (2010)

Amphiphilic peptides A(3)K, A(6)K, and A(9)K displayed an increasing propensity for nanoaggregation with increasing the size of hydrophobic alanine moiety, and the size and shape of the aggregates showed a steady transition from loose peptide stacks formed by A(3)K, long nanofibers by A(6)K, to short and narrow nanorods by A(9)K. This size and shape transition was broadly consistent with the trend predicted from interfacial packing and curvature change if these peptide surfactants were treated as conventional surfactants. The antibacterial capacity, defined by the killing of percentage of bacteria in a given time and peptide concentration, showed a strong correlation to peptide hydrophobicity, evident from both microscopic and fluorescence imaging studies. For A(9)K, the power for membrane permeation and bacterial clustering intensified with peptide concentration and incubation time. These results thus depict a positive correlation between the propensity for self-assembly of the peptides, their membrane penetration power, and bactericidal capacity. Although the exposure of A(9)K to a preformed DPPC membrane bilayer showed little structural disturbance, the same treatment to the preformed DPPG membrane bilayer led to substantial disruption of model membrane structure, a trend entirely consistent with the high selectivity observed from membrane hemolytic studies.
Mechanisms of selective motor neuron death in transgenic mouse models of motor neuron disease (1996)

To examine the mechanism(s) of disease underlying ALS, transgenic mouse models have been constructed that express aberrant neurofilaments or mutations in the abundant, cytoplasmic enzyme superoxide dismutase 1 (SOD1). In addition to progressive weakness arising from selective motor neuron death, mice expressing a modest level of a point mutant in neurofilament subunit NF-L show most of the pathologic hallmarks observed in familial and sporadic ALS, including perikaryal proximal axonal swellings, axonal degeneration, and severe skeletal muscle atrophy. Additional mice expressing familial ALS-linked mutations in the cytoplasmic enzyme SOD1, the only proven cause of ALS and which accounts for approximately 20% of familial disease, have demonstrated that at least one mutation causes disease through acquisition of an adverse property by the mutant enzyme, rather than elevation or loss of SOD1 activity. These animals not only provide a detailed look at the pathogenic progression of disease, but also represent a tool for testing hypotheses concerning the specific mechanism(s) of neuronal death and for testing therapeutic strategies.
Substance P levels in the synovium and synovial fluid from patients with rheumatoid arthritis and osteoarthritis. (1993)

Experimental results suggest that substance P (SP) may play an important role in pain and inflammation in rheumatic diseases. Measurements of SP-like immunoreactivity (SPLI) were performed in synovial fluid (SF) and synovial tissue from 40 patients with rheumatoid arthritis (RA) or osteoarthritis (OA). High levels of SPLI were found in the SF of patients with RA compared with OA. Conversely, SPLI content in synovial tissue was higher in OA than in RA, suggesting that there is an active secretory process of SPLI into the SF in RA, thus depleting SPLI stores in the synovium. Our data support the involvement of SP in the perpetuation and exacerbation of inflammation in RA, and may also explain some clinical features of this disease.