gebhart/patrepeval huggingface dataset:
Contributions of the Avian Influenza Virus HA, NA, and M2 Surface Proteins to the Induction of Neutralizing Antibodies and Protective Immunity (2009)

Highly pathogenic avian influenza virus (HPAIV) subtype H5N1 causes severe disease and mortality in poultry. Increased transmission of H5N1 HPAIV from birds to humans is a serious threat to public health. We evaluated the individual contributions of each of the three HPAIV surface proteins, namely, the hemagglutinin (HA), the neuraminidase (NA), and the M2 proteins, to the induction of HPAIV-neutralizing serum antibodies and protective immunity in chickens. Using reverse genetics, three recombinant Newcastle disease viruses (rNDVs) were engineered, each expressing the HA, NA, or M2 protein of H5N1 HPAIV. Chickens were immunized with NDVs expressing a single antigen (HA, NA, and M2), two antigens (HA+NA, HA+M2, and NA+M2), or three antigens (HA+NA+M2). Immunization with HA or NA induced high titers of HPAIV-neutralizing serum antibodies, with the response to HA being greater, thus identifying HA and NA as independent neutralization antigens. M2 did not induce a detectable neutralizing serum antibody response, and inclusion of M2 with HA or NA reduced the magnitude of the response. Immunization with HA alone or in combination with NA induced complete protection against HPAIV challenge. Immunization with NA alone or in combination with M2 did not prevent death following challenge, but extended the time period before death. Immunization with M2 alone had no effect on morbidity or mortality. Thus, there was no indication that M2 is immunogenic or protective. Furthermore, inclusion of NA in addition to HA in a vaccine preparation for chickens may not enhance the high level of protection provided by HA.
Some aspects of the problem of individual predisposition to silicosis. (1986)

Based on experimental and epidemiological data findings presented here, as well as on data of other investigators, the authors conclude that a wide interindividual variability of susceptibility to silicosis is a real phenomenon. This susceptibility depends on both intrinsic features of the host and the influence of many environmental factors. The effect of any such factor is realized at different stages of silicosis pathogenesis and in close interrelation with the influence of other factors. The necessity of multifactorial analysis is stressed, and an example of such analysis is presented.
Zinc-Mediated Synthesis of α-C-Glycosides from 1,2-Anhydroglycosides (2003)

α-C-Glycosides have been prepared by the addition of organozinc reagents to glycal epoxides. Dialkyl and diaryl zinc reagents in the presence of CF3COOH provide the corresponding α-glycosides in 53-82% yields. Organozinc chlorides RZnCl formed by the reaction RLi with zinc chloride can also be successfully applied to this coupling reaction with high α-selectivity.
Review of Regulations and Guidelines for Commercial and Noncommercial Drivers With Sleep Apnea and Narcolepsy (1995)

Studies show that persons with sleep disorders, such as sleep apnea and narcolepsy, have an increased incidence of automobile accidents. The goal of this study was to review any regulations or guidelines dealing with fitness to drive of persons with sleep disorders in all the 50 states and countries around the world. Several authorities in the United States and abroad in fact have produced guidelines or regulations stating that certain of these persons are not fit to drive. As of March 1994, only four states in the United States (Maryland, North Carolina, Oregon and Utah) had guidelines for narcolepsy, while two had guidelines for both narcolepsy and sleep apnea (California and Texas). In Maine, guidelines had been proposed for sleep apnea. In contrast, almost all Canadian provinces have guidelines for both sleep apnea and narcolepsy, as does the United Kingdom. There are, however, considerable variations in the nature of the regulations used in different states, Canadian provinces and countries. These variations are not based on scientific data. Currently the impact of these regulations on crash rates or on the practice of sleep medicine has not been assessed.
Immunogenicity to Biologics: Mechanisms, Prediction and Reduction (2012)

Currently, there is a significant rise in the development and clinical use of a unique class of pharmaceuticals termed as Biopharmaceuticals or Biologics, in the management of a range of disease conditions with, remarkable therapeutic benefits. However, there is an equally growing concern regarding development of adverse effects like immunogenicity in the form of anti-drug antibodies (ADA) production and hypersensitivity. Immunogenicity to biologics represents a significant hurdle in the continuing therapy of patients in a number of disease settings. Efforts focussed on the identification of factors that contribute towards the onset of immunogenic response to biologics have led to reductions in the incidence of immunogenicity. An in-depth understanding of the cellular and molecular mechanism underpinning immunogenic responses will likely improve the safety profile of biologics. This review addresses the mechanistic basis of ADA generation to biologics, with emphasis on the role of antigen processing and presentation in this process. The article also addresses the potential contribution of complement system in augmenting or modulating this response. Identifying specific factors that influences processing and presentation of biologic-derived antigens in different genotype and disease background may offer additional options for intervention in the immunogenic process and consequently, the management of immunogenicity to biologics.
Resistance to Integrase Inhibitors (2010)

Integrase (IN) is a clinically validated target for the treatment of human immunodeficiency virus infections and raltegravir exhibits remarkable clinical activity. The next most advanced IN inhibitor is elvitegravir. However, mutant viruses lead to treatment failure and mutations within the IN coding sequence appear to confer cross-resistance. The characterization of those mutations is critical for the development of second generation IN inhibitors to overcome resistance. This review focuses on IN resistance based on structural and biochemical data, and on the role of the IN flexible loop i.e., between residues G140-G149 in drug action and resistance.
Stochastic Resonance in the Motor System: Effects of Noise on the Monosynaptic Reflex Pathway of the Cat Spinal Cord (2007)

In sensory systems, the presence of a particular nonzero level of noise may significantly enhance the ability of an individual to detect weak sensory stimuli through a phenomenon known as stochastic resonance (SR). The aim of this study was to demonstrate if such phenomenon is also exhibited by the motor system; in particular, in the Ia-motoneuron synapse of the cat spinal cord. Monosynaptic reflexes elicited by periodic electrical stimulation to the medial gastrocnemius nerve were recorded in the L(7) ventral root (or in single motoneurons) of decerebrated cats. Random stretches (mechanical noise) were applied to the lateral gastrocnemius plus soleus muscle by means of a closed-loop mechanical stimulator-transducer. In all cats, we observed the SR phenomenon. The amplitude of the monosynaptic reflexes (or number of action potentials recorded in the motoneurons) evoked by the weak electrical stimuli applied to the medial gastrocnemius nerve were an inverted U-like function of the mechanical noise applied to the lateral gastrocnemius plus soleus muscle. A significant maximum value in the amplitude of the monosynaptic responses was reached with a particular noise amplitude value. Numerical simulations on a model of the monosynaptic reflex pathway qualitatively reproduce this stochastic resonance behavior. We conclude that the monosynaptic reflex response elicited by Ia afferents is optimized by the noisy stretching of a synergistic muscle. Our study provides the first direct demonstration that the motor system, and not only the sensory systems, exhibits the SR phenomenon.
Nitric Oxide is a Potent Relaxant of Human and Rabbit Corpus Cavernosum (1992)

Nitric oxide (NO) caused a potent, marked, and transient relaxation of precontracted strips of corpus cavernosum isolated from humans and rabbits. The relaxation response elicited by NO was very similar to the relaxation evoked by electrical field stimulation via the nonadrenergic-noncholinergic pathway. Sodium nitroprusside, nitroglycerin, and S-nitroso-N-acetylpenicillamine, which are nitrovasodilators known to generate NO, also caused marked concentration-dependent relaxation of corpus cavernosum. Relaxant responses to NO were enhanced by the cyclic GMP phosphodiesterase inhibitor M&B 22,948 and inhibited by oxyhemoglobin. Similarly, relaxation of corpus cavernosum in response to electrical field stimulation or acetylcholine was enhanced by M&B 22,948 and inhibited by oxyhemoglobin. NO stimulated cyclic GMP formation in corpus cavernosum and a close positive correlation was found between the magnitudes of relaxation and cyclic GMP formation. The data suggest that NO-elicited activation of guanylate cyclase and cyclic GMP formation represents the signal transduction mechanism responsible for relaxation and nonadrenergic-noncholinergic-mediated penile erection. These observations indicate that NO is a potent relaxant of human and rabbit corpus cavernosum and support our hypothesis that endogenous NO is the principal mediator of penile erection caused by nonadrenergic-noncholinergic stimulation.
Phase response measurement technique for waveguide grating filters (1995)

A simple interferometric technique is described which can be used to accurately measure the phase response of waveguide grating filters. A narrowband, tunable Ti:sapphire laser is used in a Michelson interferometer configuration, where light reflected from a waveguide grating filter is combined with a reference beam. The intensity of the combined beams is measured as the wavelength of the Ti:sapphire laser is tuned. The measured intensity exhibits a quasisinusoidal wavelength dependence, from which the phase response of the filter can be deduced. This method is successfully demonstrated using both an integrated optic waveguide grating filter and a bulk grating pair.
Genome‐Wide DNA Methylation Study Identifies Significant Epigenomic Changes in Osteoarthritic Cartilage (2014)

Objective To perform a genome‐wide DNA methylation study to identify DNA methylation changes in osteoarthritic (OA) cartilage tissue. Methods The contribution of differentially methylated genes to OA pathogenesis was assessed by bioinformatic analysis, gene expression analysis, and histopathologic severity correlation. Genome‐wide DNA methylation profiling of &gt;485,000 methylation sites was performed on eroded and intact cartilage from within the same joint of 24 patients undergoing hip arthroplasty for OA. Genes with differentially methylated CpG sites were analyzed to identify overrepresented gene ontologies, pathways, and upstream regulators. The messenger RNA expression of a subset of differentially methylated genes was analyzed by reverse transcription–polymerase chain reaction. Histopathology was graded by modified Mankin score and correlated with DNA methylation. Results We identified 550 differentially methylated sites in OA. Most (69%) were hypomethylated and enriched among gene enhancers. We found differential methylation in genes with prior links to OA, including RUNX1 , RUNX2 , DLX5 , FURIN , HTRA1 , FGFR2 , NFATC1 , SNCAIP , and COL11A2 . Among these, RUNX1 , HTRA1 , FGFR2 , and COL11A2 were also differentially expressed. Furthermore, we found differential methylation in approximately one‐third of known OA susceptibility genes. Among differentially methylated genes, upstream regulator analysis showed enrichment of TGFB1 ( P = 4.40 × 10 −5 ) and several microRNAs including miR‐128 ( P = 4.48 × 10 −13 ), miR‐27a ( P = 4.15 × 10 −12 ), and miR‐9 ( P = 9.20 × 10 −10 ). Finally, we identified strong correlations between 20 CpG sites and the histologic Mankin score in OA. Conclusion Our data implicate epigenetic dysregulation of a host of genes and pathways in OA, including a number of OA susceptibility genes. Furthermore, we identified correlations between CpG methylation and histologic severity in OA.
The effect of odors on the behavior of adult Aedes aegypti and some factors limiting responsiveness (1972)

Caged adult Aedes aegypti aggregated at the source of ethyl ether soluble honey odors in relatively still air. Arrival at the source of odor was not random. The volatile substances stimulated locomotory activity in mosquitoes settled in the cage. The majority of these active individuals arrived at the odor source and did so within a mean period of 1.5 min. At the same time, arrivals at a visually similar, comparably situated control were rare. Insects probed at the odor source and remained in the area of highest odor concentration by turning at the boundary to a lower concentration. Habituation occurred within about 12 min of exposure to the odor and the aggregation was then dispersed.Male and female mosquitoes responded to honey odors equally well. Responsiveness increased with time of food deprivation and feeding raised the threshold of response.Mechanisms of orientation to the odor are discussed.
Marked improvement of cytotoxic effects induced by docetaxel on highly metastatic and androgen-independent prostate cancer cells by downregulating macrophage inhibitory cytokine-1 (2013)

These data suggest that the downregulation of MIC-1 may constitute a potential therapeutic strategy for improving the efficacy of current docetaxel-based chemotherapies, eradicating the total mass of PC cells and thereby preventing disease relapse and the death of PC patients.
β-Peptide Foldamers:  Robust Helix Formation in a New Family of β-Amino Acid Oligomers (1996)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTβ-Peptide Foldamers: Robust Helix Formation in a New Family of β-Amino Acid OligomersDaniel H. Appella, Laurie A. Christianson, Isabella L. Karle, Douglas R. Powell, and Samuel H. GellmanView Author Information Department of Chemistry, University of Wisconsin Madison, Wisconsin 53706-1396 Laboratory for the Structure of Matter Naval Research Laboratory, Washington, D.C. 20375-5341 Cite this: J. Am. Chem. Soc. 1996, 118, 51, 13071–13072Publication Date (Web):December 25, 1996Publication History Received19 September 1996Published online25 December 1996Published inissue 1 January 1996https://doi.org/10.1021/ja963290lCopyright © 1996 American Chemical SocietyRIGHTS & PERMISSIONSArticle Views5015Altmetric-Citations578LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit Read OnlinePDF (125 KB) Get e-AlertsSupporting Info (1)»Supporting Information Supporting Information SUBJECTS:Amides,Conformation,Molecules,Noncovalent interactions,Oligomers Get e-Alerts
Cationic Polymer Modified Mesoporous Silica Nanoparticles for Targeted siRNA Delivery to HER2+ Breast Cancer (2015)

<i>In vivo</i> delivery of siRNAs designed to inhibit genes important in cancer and other diseases continues to be an important biomedical goal. We now describe a new nanoparticle construct that has been engineered for efficient delivery of siRNA to tumors. The construct is comprised of a 47-nm mesoporous silica nanoparticle (MSNP) core coated with a cross-linked PEI-PEG copolymer, carrying siRNA against the HER2 oncogene, and coupled to the anti-HER2 monoclonal antibody (trastuzumab). The construct has been engineered to increase siRNA blood half-life, enhance tumor-specific cellular uptake, and maximize siRNA knockdown efficacy. The optimized anti-HER2-nanoparticles produced apoptotic death in HER2 positive (HER2<sup>+</sup>) breast cancer cells grown <i>in vitro</i>, but not in HER2 negative (HER2<sup>-</sup>) cells. One dose of the siHER2-nanoparticles reduced HER2 protein levels by 60% in trastuzumab-resistant HCC1954 xenografts. Multiple doses administered intravenously over 3 weeks significantly inhibited tumor growth (p < 0.004). The siHER2-nanoparticles have an excellent safety profile in terms of blood compatibility and low cytokine induction, when exposed to human peripheral blood mononuclear cells. The construct can be produced with high batch-to-batch reproducibility and the production methods are suitable for large-scale production. These results suggest that this siHER2-nanoparticle is ready for clinical evaluation.
Cellular dosimetry: absorbed fractions for monoenergetic electron and alpha particle sources and S-values for radionuclides uniformly distributed in different cell compartments. (1994)

With the absorbed fractions and S-values in hand, along with experimentally determined information on the biokinetics and subcellular distribution of the radionuclides, the cellular self-absorbed dose can be conveniently calculated.
Fourier transform infrared studies of secondary structure and orientation of pulmonary surfactant SP-C and its effect on the dynamic surface properties of phospholipids (1991)

SP-C, a highly hydrophobic, 3.7-kDa protein constituent of lung surfactant, has been isolated from bovine lung lavage, purified, and reconstituted into binary lipid mixtures of 1,2-dipalmitoyl-phosphatidylcholine (DPPC) and 1,2-dipalmitoylphosphatidylglycerol (DPPG). Fourier transform infrared (FT-IR) spectroscopy has been applied to examine SP-C secondary structure, the average orientation of alpha-helical segments relative to the bilayer normal in membrane films, and the effect of protein on the thermotropic properties of the phospholipid acyl chains. In addition, dynamic surface measurements were made on phospholipid films at the A/W interface in the presence and absence of SP-C. SP-C (0.5 mol %) was found to possess about 60% alpha-helical secondary structure in lipid vesicles. Higher levels (1.5 mol %) of SP-C resulted in a slight increase of beta-forms, possibly resulting from protein aggregation. The helical segments exhibited an average angle of orientation of about 24 degrees with respect to the bilayer normal, suggesting a trans-bilayer orientation of the peptide. The observation that 70% of the peptide bond hydrogens are hard to exchange in D2O further reflects the hydrophobic nature of the molecule. SP-C produced little effect on the thermotropic properties of the binary lipid mixture, as measured from acyl chain C-H and C-D stretching frequencies. However, the presence of 1 mol % protein markedly reduced the viscance and increased the elasticity of surface films suggesting a mechanism by which SP-C facilitates the spreading of phospholipids on an aqueous surface. The possible physiological consequences of these observations are discussed.
Topology optimization of structures using ant colony optimization (2009)

A modified ACO algorithm that derives from specific definition of pheromone and cooperation mechanism between ants was applied for solving topology optimization problem of structure. Mesh topology of finite element model for structure was treated as possible paths for ant's movement. A tour on mesh topology map for seeking food finished by ant is transformed into a structure and the finite element method was applied to analyze the structure for calculating pheromone deposited on the path. The amount of accumulated pheromone deposited on every element by different ants was used to find optimum structural design. From the results studied in this paper, the purposed ACO algorithm provides as alternate optimization method that has high potential in finding the best design for topology optimization of structure successfully and efficiently.
Expression of enzymatically active reverse transcriptase in Escherichia coli. (1985)

Reverse transcriptase of murine retroviruses is a monomeric protein of approximately 80,000 daltons, which is encoded by the central portion of the viral pol gene. To prepare large quantities of the enzyme, we have constructed gene fusions between the trpE gene and portions of the pol gene of Moloney murine leukemia virus. The inserted pol gene sequences include the entire coding region for the mature enzyme and various amounts of additional coding sequences. Many of these constructs express high levels of reverse transcriptase activity even though the NH2 and COOH termini of the protein product only approximate the correct termini of the authentic protein.
Hydrogen Production by Plasma Electrolysis (2006)

Preliminary data from controlled experiments indicate that in plasma electrolysis, metallic electrodes do not have to be immersed in water to produce hydrogen and oxygen as in the case of traditional electrolysis. Instead, the electrodes can interact with water through atmospheric pressure plasmas located between the electrode tips and the water surface. Experiments and spectral analysis of the light emitted by the plasmas as well as mass spectroscopic testing of gases from a region near the negative electrode, clearly indicate that the plasma associated with the negative electrode evolves hydrogen from the water. When a single plasma electrode was used in conjunction with a conventional immersed metal electrode, vigorous bubbling was observed at the immersed electrode. In very broad but fundamental terms, the advantage of this method is that high velocity transport of hydrogen through gas phase plasma-bounding regions (i.e., plasma sheaths) might replace low-speed diffusion through liquid phase that is currently used in conventional electrolysis. This process is likely to increase the rate of generation and collection of hydrogen over those of current electrolysis methods with high potential for integration into fuel cell systems and modular units for augmentation of small-scale power systems for distributed electricity generation.
A randomized trial to assess the pharmacodynamics and pharmacokinetics of a single dose of an extended-release aspirin formulation (2015)

Both ASA formulations showed dose-dependent antiplatelet activity. Compared with the IR-ASA, ER-ASA released active drug more slowly, resulting in prolonged absorption and lower systemic drug concentrations, which is expected for an ER (24-h) formulation.