gebhart/patrepeval huggingface dataset:
Dietary Sulforaphane-Rich Broccoli Sprouts Reduce Colonization and Attenuate Gastritis inHelicobacter pylori–Infected Mice and Humans (2009)

The isothiocyanate sulforaphane [SF; 1-isothiocyanato-4(R)-methylsulfinylbutane] is abundant in broccoli sprouts in the form of its glucosinolate precursor (glucoraphanin). SF is powerfully bactericidal against Helicobacter pylori infections, which are strongly associated with the worldwide pandemic of gastric cancer. Oral treatment with SF-rich broccoli sprouts of C57BL/6 female mice infected with H. pylori Sydney strain 1 and maintained on a high-salt (7.5% NaCl) diet reduced gastric bacterial colonization, attenuated mucosal expression of tumor necrosis factor-alpha and interleukin-1beta, mitigated corpus inflammation, and prevented expression of high salt-induced gastric corpus atrophy. This therapeutic effect was not observed in mice in which the nrf2 gene was deleted, strongly implicating the important role of Nrf2-dependent antioxidant and anti-inflammatory proteins in SF-dependent protection. Forty-eight H. pylori-infected patients were randomly assigned to feeding of broccoli sprouts (70 g/d; containing 420 micromol of SF precursor) for 8 weeks or to consumption of an equal weight of alfalfa sprouts (not containing SF) as placebo. Intervention with broccoli sprouts, but not with placebo, decreased the levels of urease measured by the urea breath test and H. pylori stool antigen (both biomarkers of H. pylori colonization) and serum pepsinogens I and II (biomarkers of gastric inflammation). Values recovered to their original levels 2 months after treatment was discontinued. Daily intake of sulforaphane-rich broccoli sprouts for 2 months reduces H. pylori colonization in mice and improves the sequelae of infection in infected mice and in humans. This treatment seems to enhance chemoprotection of the gastric mucosa against H. pylori-induced oxidative stress.
Suppression of postischemic epileptiform activity with MK‐801 improves neural outcome in fetal sheep (1992)

To determine the effect of suppression of epileptiform activity that develops after hypoxic-ischemic injury in the immature brain, chronically instrumented near-term fetal sheep (119-133 days) were subjected to 30 minutes of complete cerebral ischemia: 6 were given a 0.3-mg/kg bolus of MK-801 at 6 hours after the insult followed by continuous infusion of 1 mg/kg over the next 36 hours, and were compared to 6 control sheep. Electrocorticographic activity and edema within the parasagittal region of the cortex were quantified with real-time spectral analysis and impedance measurements, respectively. Histological outcome was assessed 72 hours later. The intense epileptiform activity seen from 9 +/- 2 to 30 +/- 3 hours in the control group was completely suppressed in the MK-801-treated group. The onset of secondary cortical edema was delayed from 9.4 +/- 1.1 hours to 14.8 +/- 0.7 hours (p < 0.01). Neuronal damage was reduced, particularly in the lateral cortex and hippocampus (p < 0.05). Infarction of the parasagittal cortex was not prevented. These results suggest that N-methyl-D-aspartate-mediated epileptiform activity that develops after a global hypoxic-ischemic insult worsens neuronal outcome in the immature brain.
Aromatic Nonpolar Nucleosides as Hydrophobic Isosteres of Pyrimidines and Purine Nucleosides (1994)

Described are the design, synthesis, and structures of three nonpolar nucleoside isosteres to be used as probes of noncovalent bonding in DNA and as isosteric replacements for the natural nucleosides in designed nucleic acid structures. Reaction of substituted aryl Grignards with 3',5'-bis-O-toluoyl-α-deoxyibofuranosyl chloride and subsequent deprotection with sodium methoxide in methanol afforded the two β-C-nucleoside pyrimidine analogs 1 and 2. The dimethylindolyl nucleoside 3, a purine isostere, was obtained by a nucleophilic displacement on α-chlorodeoxyribofuranose by the sodium salt of 4,6-dimethylindole, followed by deprotection. Regio- and stereochemistry of the products were established with NOE difference spectra and (1)H NMR splitting patterns. Analogs 1 and 2 are nonpolar isosteres of thymidine, and nucleoside 3 is an isostere of 2-aminodeoxyadenosine, the triply-bonded Watson-Crick partner of thymidine. Semiempirical AM1 calculations were carried out to provide bond length information to assess structural similarities between the isosteres and their natural counterparts.
Infusions of Donor Leukocytes to Treat Epstein-Barr Virus-Associated Lymphoproliferative Disorders after Allogeneic Bone Marrow Transplantation (1994)

In a small number of patients, infusions of unirradiated donor leukocytes were an effective treatment for EBV-associated lymphoproliferative disease that arose after allogeneic bone marrow transplantation.
NNAlign: a platform to construct and evaluate artificial neural network models of receptor–ligand interactions (2017)

Peptides are extensively used to characterize functional or (linear) structural aspects of receptor-ligand interactions in biological systems, e.g. SH2, SH3, PDZ peptide-recognition domains, the MHC membrane receptors and enzymes such as kinases and phosphatases. NNAlign is a method for the identification of such linear motifs in biological sequences. The algorithm aligns the amino acid or nucleotide sequences provided as training set, and generates a model of the sequence motif detected in the data. The webserver allows setting up cross-validation experiments to estimate the performance of the model, as well as evaluations on independent data. Many features of the training sequences can be encoded as input, and the network architecture is highly customizable. The results returned by the server include a graphical representation of the motif identified by the method, performance values and a downloadable model that can be applied to scan protein sequences for occurrence of the motif. While its performance for the characterization of peptide-MHC interactions is widely documented, we extended NNAlign to be applicable to other receptor-ligand systems as well. Version 2.0 supports alignments with insertions and deletions, encoding of receptor pseudo-sequences, and custom alphabets for the training sequences. The server is available at http://www.cbs.dtu.dk/services/NNAlign-2.0.
Role of tachykinins in airway responses to ozone in rats (1998)

Previous studies that used neonatal capsaicin (Cap) treatment to ablate C fibers indicate that C fibers act to inhibit lung damage and airway hyperresponsiveness after ozone (O3) exposure in rats. The purpose of this study was to determine 1) the role of tachykinins in these protective effects and 2) whether differences in minute ventilation (VE) during O3 exposure might account for the effect of Cap. In the first study, male Sprague-Dawley rats were exposed to 1 part/million O3 or air for 3 h. Four hours later, a bronchoalveolar lavage (BAL) was performed or airway responsiveness was measured. Rats were treated with CP-99994 and SR-48968, selective neurokinin-1- and -2-receptor antagonists, respectively, or with vehicle (Veh). O3 caused an increase in the number of neutrophils recovered from BAL fluid in both the Veh-treated and tachykinin-receptor antagonist (TKRA)-treated rats, but the number of neutrophils was approximately twofold greater in the TKRA-treated rats. In contrast, TKRA treatment had no effect on baseline pulmonary mechanics or airway responsiveness. After O3 exposure, the number of neutrophils in BAL fluid was also greater in Cap- than in Veh-treated rats. O3 reduced VE in both Veh- and Cap-treated rats, but the response was greater (reduction of 44.7 +/- 3.7 vs. 27.8 +/- 6.8%) and occurred earlier (10 vs. 70 min) in Cap- than in Veh-treated rats (P < 0.02). These results suggest that tachykinins mediate protective effects of C fibers against O3-induced lung inflammation. The results also indicate that the more pronounced effect of O3 on BAL neutrophils in Cap-treated rats is not the result of a greater inhaled dose of O3 resulting from greater VE.
Covalent Immobilization of Proteins onto (Maleic Anhydride-alt-methyl Vinyl Ether) Copolymers:  Enhanced Immobilization of Recombinant Proteins (1998)

Two genetically modified HIV-1 capsid p24 proteins, RH24 and RH24K, were covalently bound to maleic anhydride-alt-methyl vinyl ether (MAMVE) copolymer, under aqueous conditions. We demonstrated that the addition of a six lysine unit tag at the COOH-terminus of RH24K greatly improved the grafting reaction which could take place under many different experimental conditions. The course of the reaction was controlled by electrostatic attractive forces between the protein and the negatively charged polymer, as the chemical binding was more efficient at low ionic strength. The maximum loading capacity of the polymer depended on whether the protein bore the lysine tag (RH24K) or not (RH24). Twenty-four molecules of RH24 could be immobilized per polymer chain and 49 for RH24K. Such a difference could be explained by a difference of orientation of the protein on the polymer, side-on for RH24 and end-on for RH24K to account for the observed high packing density.
Ubiquitin‐proteasome system alterations in a striatal cell model of huntington's disease (2007)

Huntington's disease (HD) is a progressive, autosomal dominant neurodegenerative disease caused by an abnormally expanded CAG repeat in the HD gene. Ubiquitylated aggregates containing mutant huntingtin protein in neurons are hallmarks of HD. Misfolded mutant huntingtin monomers, oligomers, or aggregates may be a result of, and cause, ubiquitin- proteasome dysfunction. To investigate the ubiquitin-proteasome system we designed a series of firefly luciferase reporters targeted selectively to different points along this pathway. These reporters were used to monitor ubiquitin-proteasome system function in a striatal cell culture model of HD. Ubiquitylation processes were not reduced in mutant huntingtin cells but recognition or degradation of ubiquitylated substrates was decreased. We also found mutant huntingtin expressing cells had slight but significant decreases in chymotrypsin-like and caspase-like activities, and an unexpected increase in trypsin-like activity of the proteasome core. General proteasome core inhibitors, as well as selective caspase-like activity inhibitors, were less effective in mutant cells. Finally, treatment with 3-nitropropionic acid, a succinate dehydrogenase inhibitor, had opposite effects on the ubiquitin-proteasome system with activation in wild-type and decreased activity in mutant huntingtin expressing cells. The results of these experiments show clearly selective disruption of the ubiquitin-proteasome system in this cell culture model of HD. The high throughput tools that we have designed and optimized will also be useful in identifying compounds that alter ubiquitin-proteasome system function and to investigate other neurodegenerative diseases such Alzheimer's disease and Parkinson's disease.
DNASTAR's Lasergene Sequence Analysis Software (2003)

Lasergene's eight modules provide tools that enable users to accomplish each step of sequence analysis, from trimming and assembly of sequence data, to gene discovery, annotation, gene product analysis, sequence similarity searches, sequence alignment, phylogenetic analysis, oligonucleotide primer design, cloning strategies, and publication of the results. The Lasergene software suite provides the functions and customization tools needed so that users can perform analyses the software writers never imagined.
Cytokines and Soluble Adhesion Molecules in Sickle Cell Anemia Patients during Hydroxyurea Therapy (1998)

Hydroxyurea (HU) induces HbF production and can reduce painful crises in some patients with sickle cell anemia (SS). However, HbF induction alone cannot explain the beneficial effect of HU treatment as some patients experience clinical improvement while showing only minor increases in HbF. Other actions of HU, in particular its effects on vascular endothelium, adhesion molecule expression and cytokine production may also play a role in the final therapeutic outcome. In order to analyze these effects we studied the levels of interleukin-3 (IL-3), interleukin-6, granulocyte-macrophage colony-stimulating factor, erythropoietin, stem cell factor, soluble vascular adhesion molecule-1, soluble intercellular adhesion molecule-1, soluble E-selectin and soluble P-selectin in 7 SS patients before and during 5 months of HU treatment. Use of HU seems to have no detectable effect on soluble adhesion molecules, but the steady state levels of soluble vascular adhesion molecule-1 are enhanced in SS patients compared to normal controls. Of the cytokines studied, only IL-3 showed an increase during therapy, suggesting HU may induce early erythroid progenitors capable of producing HbF by a direct or indirect effect on IL-3 production. Remarkably, the steady state stem cell factor levels in sickle cell patients seemed to be decreased compared to healthy controls.
Peptidomimetics derived from natural products (1993)

Although much has been written in recent years about rational drug design, no drug has been designed de novo, that is, without using a natural substrate or inhibitor or screening lead as a starting point. Instead, as we have seen, medicinal chemists continue to depend upon serendipitous discovery of novel biological activities and novel chemical entities for structures on which to begin work. What rational drug design really means at present is rational drug discovery and rational optimization. These result from the application of modern structural and mechanistic biochemistry, and good synthetic chemistry, to obtain structures with the desired spectrum of biological activities. Traditionally, lead compounds were discovered in plant and animal extracts, and more recently in microorganisms and chemical libraries. These traditional approaches continue, but are augmented by advances in molecular biology, which now provide pure proteins in quantity for screening and structure determination, as well as for characterization by modern biophysical methods. Remarkably, x-ray and NMR methods can now provide the most important information needed to design new drugs, that is, the conformations of ligands bound to target proteins. Approaches to identifying possible ligands based only on the knowledge of the enzyme active site are being developed. Some of these, such as CAVEAT, have been recently reviewed. In spite of these impressive gains, de novo design of new drugs will not be achieved until we learn how to logically build specific inhibitors of a target enzyme knowing only the protein sequence of the enzyme or the amino acid sequence of the messenger substances. We have a long way to go, because by this very rigorous definition, even the successful design of a new nonpeptide drug beginning with enzyme-ligand NMR or x-ray structure constitutes rational optimization. However, as this article has illustrated, we have made great progress. Some of the current and futuristic approaches to drug design are shown in Fig. 8. Development of useful enzyme inhibitors, designed by knowing the enzyme catalytic mechanism or discovered by screening for natural inhibitors, is a very successful rational method. Discovery of receptor antagonists by screening protocols is also productive.(ABSTRACT TRUNCATED AT 400 WORDS)
Construction and functional study of a novel anti HER2/neu-hTNF-alpha immunotoxin (2005)

HER2/neu is an attractive target for tumor therapy since its overexpression in a number of tumors. In order to enhance the cytotoxicity of anti-HER2/neu antibody, and the specificity of TNF-alpha for tumor cell, a fusion gene of antiHER2-hTNF-alpha was constructed. The recombinant fusion protein was produced in E.coli, and their refolding has done through affinity chromatography on a His-column. The ELISA assay showed that antiHER2-hTNF-alpha specifically bound to HER2/neu expressing SKOV-3 and MCF-7 cells, but it did not recognize the HER2/neu negative cells A375. In vitro study, it was found that antiHER2-hTNF-alpha inhibited the proliferation of SKOV-3 and MCF-7 cells, whereas it did not effect on the A375. These studies suggest that the recombinant antiHER2-hTNF-alpha immunotoxin has a potential application in HER2/neu expressing tumor therapy.
Three-dimensional object recognition from single two-dimensional images (1987)

A computer vision system has been implemented that can recognize three-dimensional objects from unknown viewpoints in single gray-scale images. Unlike most other approaches, the recognition is accomplished without any attempt to reconstruct depth information bottom-up from the visual input. Instead, three other mechanisms are used that can bridge the gap between the two-dimensional image and knowledge of three-dimensional objects. First, a process of perceptual organization is used to form groupings and structures in the image that are likely to be invariant over a wide range of viewpoints. Second, a probabilistic ranking method is used to reduce the size of the search space during model-based matching. Finally, a process of spatial correspondence brings the projections of three-dimensional models into direct correspondence with the image by solving for unknown viewpoint and model parameters. A high level of robustness in the presence of occlusion and missing data can be achieved through full application of a viewpoint consistency constraint. It is argued that similar mechanisms and constraints form the basis for recognition in human vision.
PCR analysis of cytokine induction profiles associated with mouse strain variation in susceptibility to pulmonary fibrosis. (1993)

Susceptibility of mice to the induction of pulmonary fibrosis by bleomycin sulfate is inbred strain dependent, with C57BL/6 mice exhibiting high sensitivity to the drug and BALB/c mice demonstrating a resistant phenotype. The lungs of bleomycin treated C57BL/6J and BALB/cBy mice were analyzed for their mRNA expression level of a panel of cytokines using a semi-quantitative polymerase chain reaction (SQ-PCR) assay. Transforming growth factor-beta 1 (TGF-beta 1) mRNA was found to increase sevenfold by 5 days after bleomycin treatment of C57BL/6J (sensitive) mice. BALB/cBy (resistant) animals demonstrated a lower level of TGF-beta 1 mRNA induction, approximately threefold, after bleomycin administration. Analysis of interleukin-1 beta (IL-1 beta) mRNA levels also revealed a difference between the two strains, with BALB/cBy mice expressing approximately fourfold higher IL-1 beta mRNA levels than C57BL/6J mice. This result suggested possible protection by IL-1 beta. Analysis of (C57BL/6JxBALB/cBy)F1 hybrids, which are shown in this report to be sensitive to bleomycin-induced fibrosis, revealed a high IL-1 beta mRNA level, similar to that in the resistant parent. Thus, the observed strain variation in the level of IL-1 beta mRNA is not associated with differences in susceptibility to the induction of pulmonary fibrosis. In contrast, strain variation in interleukin-6 (IL-6) mRNA levels was observed that was completely concordant with the segregation of susceptibility phenotypes between the parental and F1 strains. This result indicates a possible association between sensitivity to bleomycin-induced fibrosis and inducibility of IL-6 mRNA upon drug treatment. Analysis of TGF-beta 2, interferon-gamma, interleukin-2, interleukin-3, and interleukin-4 (IL-4) mRNA showed no detectable strain variation in steady state mRNA levels in the lung as a consequence of bleomycin treatment. In contrast, the level of IL-4 receptor mRNA was induced to a higher degree in both sensitive groups (C57BL/6J and F1) than in resistant mice (BALB/cBy). Therefore, modulation of the IL-4 response, not at the level of IL-4 but through regulation of the IL-4 receptor, may play a role in pulmonary fibrogenesis.
Unsupervised Semantic Parsing of Video Collections (2015)

Human communication typically has an underlying structure. This is reflected in the fact that in many user generated videos, a starting point, ending, and certain objective steps between these two can be identified. In this paper, we propose a method for parsing a video into such semantic steps in an unsupervised way. The proposed method is capable of providing a semantic "storyline" of the video composed of its objective steps. We accomplish this using both visual and language cues in a joint generative model. The proposed method can also provide a textual description for each of the identified semantic steps and video segments. We evaluate this method on a large number of complex YouTube videos and show results of unprecedented quality for this intricate and impactful problem.
Investigation of Thick-Film Polyaniline-Based Conductimetric pH Sensors for Medical Applications (2009)

This paper reports on the development and testing of a polyaniline-based conductimetric pH sensor. The sensor functions successfully in both the pH range for stomach acid (pH1.0-pH2.0) and for human blood (pH7.0-pH8.0). Experiments were performed by exposing the sensors to buffer solutions with pH values in the ranges identified. The sensors demonstrated reproducible and repeatable results with little hysteresis being recorded between experiments, along with a response time of approximately 1 min in acidic solutions and 2 min in buffers with pH values in the blood pH range. In the case of measurements made in the blood pH range, a novel memory effect was observed, which corresponds to a permanent ldquorecordingrdquo of the pH measurement into the electrical characteristics of the film. This memory effect only applies to measurements made in alkaline pH ranges and is due to the deprotonation of the polyaniline material in the sensing layer. The sensor reported in this paper has the potential to be a more economically viable option when compared to other approaches being used for commercial applications.
Prevention of Umbilical Artery Catheter Clots withHeparinized Infusates (1981)

49 neonates requiring umbilical artery catheters (UACs) were randomly assigned to receive standard or heparin-containing infusates. 3 of 23 (13%) of the patients receiving heparin had catheters removed because they became functionally occluded compared to 15 of 26 (58%) in the control group (p less than 0.005). 4 of 13 (31%) single injection aortograms obtained in control infants demonstrated thrombi, compared to none of 7 in the heparin group. 1 patient in the heparin group had an aortic clot demonstrated at post-mortum examination. There were neither clinical coagulopathies nor abnormalities of partial thromboplastin time attributable to the administration of heparinized fluids. Heparinization of UAC infusates appears to be a safe method of reducing the risk of catheter occlusion. Heparin effect on large vessel clot risk remains unproven.