gebhart/patrepeval huggingface dataset:
Evidence that epithelial glycoprotein 330/megalin mediates uptake of polybasic drugs. (1995)

Glycoprotein 330 (gp330) is an endocytic receptor expressed in the renal proximal tubules and some other absorptive epithelia, e.g., in the inner ear. The present study shows that the antifibrinolytic polypeptide, aprotinin, and the nephro- and ototoxic antibiotics, aminoglycosides, and polymyxin B compete for binding of 125I-urokinase-plasminogen activator inhibitor type-1 complexes to purified rabbit gp330. Half maximal inhibition was measured at 4 microM for aprotinin, 50 microM for gentamicin, and 0.5 microM for polymyxin B. Drug binding to gp330 was validated by equilibrium dialysis of [3H] gentamicin-gp330 incubations and binding/uptake studies in rat proximal tubules and gp330-expressing L2 carcinoma cells. Analyses of mutant aprotinins expressed in Saccharomyces cerevisiae revealed that basic residues are essential for the binding to gp330 and renal uptake. The polybasic drugs also antagonized ligand binding to the human alpha 2-macroglobulin receptor. However, the rapid glomerular filtration of the drugs suggests kidney gp330 to be the quantitatively most important target. In conclusion, a novel role of gp330 as a drug receptor is demonstrated. The new insight into the mechanism of epithelial uptake of polybasic drugs might provide a basis for future design of drugs with reduced toxicity.
Analogues of luteinizing hormone-releasing hormone containing cytotoxic groups. (1992)

In an attempt to produce better cytotoxic analogues, chemotherapeutic antineoplastic radicals including an alkylating nitrogen mustard derivative of D-phenylalanine (D-melphalan), reactive cyclopropane, anthraquinone derivatives [2-(hydroxymethyl)anthraquinone and the anticancer antibiotic doxorubicin], and an antimetabolite (methotrexate) were coupled to suitably modified agonists and antagonists of luteinizing hormone-releasing hormone (LH-RH). Analogues with D-lysine6 and D-ornithine6 or N epsilon-(2,3-diaminopropionyl)-D-lysine and N delta-(2,3-diaminopropionyl)-D-ornithine were used as carriers for one or two cytotoxic moieties. The enhanced biological activities produced by the incorporation of D amino acids into position 6 of the agonistic analogues were further increased by the attachment of hydrophobic cytotoxic groups, resulting in compounds with 10-50 times higher activity than LH-RH. Most of the monosubstituted agonistic analogues showed high affinities for the membrane receptors of human breast cancer cells, while the receptor binding affinities of peptides containing two cytotoxic side chains were lower. Antagonistic carriers [Ac-D-Nal(2)1,D-Phe(4Cl)2,D-Trp3,Arg5,D-Lys6,D-Ala10] LH-RH [where Nal(2) is 3-(2-naphthyl)alanine], [Ac-D-Nal(2)1,D-Phe(4Cl)2,D-Trp3,Arg5,N epsilon-(2,3-diaminopropionyl)-D-Lys6,D-Ala10]LH-RH, and their D-Pal(3)3 homologs [Pal(3) is 3-(3-pyridyl)alanine] as well as [Ac-D-Nal(2)1,D-Phe(4Cl)2,D-Pal(3)3,Tyr5,N epsilon-(2,3-diamino-propionyl)-D-Lys6,D-Ala10]LH-RH were linked to cytotoxic compounds. The hybrid molecules inhibited ovulation in rats at doses of 10 micrograms and suppressed LH release in vitro. The receptor binding of cytotoxic analogues was decreased compared to the precursor peptides, although analogues with 2-(hydroxymethyl)anthraquinone hemiglutarate had high affinities. All of the cytotoxic analogues tested inhibited [3H]thymidine incorporation into DNA in cultures of human breast and prostate cancer cell lines. Some cytotoxic analogues also significantly suppressed the growth of mammary and prostate cancers in vivo in animal models.
Antibody-Dependent Enhancement of Virus Infection and Disease (2003)

In general, virus-specific antibodies are considered antiviral and play an important role in the control of virus infections in a number of ways. However, in some instances, the presence of specific antibodies can be beneficial to the virus. This activity is known as antibody-dependent enhancement (ADE) of virus infection. The ADE of virus infection is a phenomenon in which virus-specific antibodies enhance the entry of virus, and in some cases the replication of virus, into monocytes/macrophages and granulocytic cells through interaction with Fc and/or complement receptors. This phenomenon has been reported in vitro and in vivo for viruses representing numerous families and genera of public health and veterinary importance. These viruses share some common features such as preferential replication in macrophages, ability to establish persistence, and antigenic diversity. For some viruses, ADE of infection has become a great concern to disease control by vaccination. Consequently, numerous approaches have been made to the development of vaccines with minimum or no risk for ADE. Identification of viral epitopes associated with ADE or neutralization is important for this purpose. In addition, clear understanding of the cellular events after virus entry through ADE has become crucial for developing efficient intervention. However, the mechanisms of ADE still remain to be better understood.
General nonlinear framework for the analysis of gene interaction via multivariate expression arrays (2000)

A cDNA microarray is a complex biochemical-optical system whose purpose is the simultaneous measurement of gene expression for thousands of genes. In this paper we propose a general statistical approach to finding associations between the expression patterns of genes via the coefficient of determination. This coefficient measures the degree to which the transcriptional levels of an observed gene set can be used to improve the prediction of the transcriptional state of a target gene relative to the best possible prediction in the absence of observations. The method allows incorporation of knowledge of other conditions relevant to the prediction, such as the application of particular stimuli or the presence of inactivating gene mutations, as predictive elements affecting the expression level of a given gene. Various aspects of the method are discussed: prediction quantification, unconstrained prediction, constrained prediction using ternary perceptrons, and design of predictors given small numbers of replicated microarrays. The method is applied to a set of genes undergoing genotoxic stress for validation according to the manner in which it points toward previously known and unknown relationships. The entire procedure is supported by software that can be applied to large gene sets, has a number of facilities to simplify data analysis, and provides graphics for visualizing experimental data, multiple gene interaction, and prediction logic.
Multiple Actions of Recombinant Activin-Ain Vivo (1989)

Activin stimulates the secretion of FSH from cultured pituitary cells and enhances the differentiation of erythroid progenitors in vitro. The role of activin in the physiological regulation of either process, however, is unknown. We report here that systemic administration of recombinant human activin-A to immature female rats caused a marked increase in serum FSH levels. In addition, in ovariectomized estrogen-treated rats recombinant human activin-A induced a small but statistically significant increase in the circulating concentrations of red blood cells and hemoglobin. These data demonstrate the efficacy of activin in vivo, supporting the hypothesis that this protein is an important regulator of gonadotropic and erythroid function.
The theory of spherical and ellipsoidal harmonics (1955)

Preface 1. The transformation of Laplaces's equation 2. The solution of Laplace's equation in polar coordinates 3. The Legendres associated functions 4. Spherical harmonics 5. Spherical harmonics of general type 6. Approximate values of the generalized Legendres functions 7. Representation of functions by series 8. The addition theorems for general Legendres functions 9. The zeros of Legendres functions and associated functions 10. Harmonics for spaces bounded by surfaces of revolution 11. Ellipsoidal harmonics List of authors quoted General index.
ISRE-Reporter Mouse Reveals High Basal and Induced Type I IFN Responses in Inflammatory Monocytes (2018)

Type I and type III interferons (IFNs) are critical for controlling viral infections. However, the precise dynamics of the IFN response have been difficult to define in vivo. Signaling through type I IFN receptors leads to interferon-stimulated response element (ISRE)-dependent gene expression and an antiviral state. As an alternative to tracking IFN, we used an ISRE-dependent reporter mouse to define the cell types, localization, and kinetics of IFN responding cells during influenza virus infection. We find that measurable IFN responses are largely limited to hematopoietic cells, which show a high sensitivity to IFN. Inflammatory monocytes display high basal IFN responses, which are enhanced upon infection and correlate with infection of these cells. We find that inflammatory monocyte development is independent of IFN signaling; however, IFN is critical for chemokine production and recruitment following infection. The data reveal a role for inflammatory monocytes in both basal IFN responses and responses to infection.
BladeCenter networking (2005)

The IBM eServer™ BladeCenter® system physically consolidates the server and network into a common chassis. It was introduced as a new server architecture that provides many benefits over the traditional data center model of clustered independent systems linked by a network fabric. This paper describes the BladeCenter networking architecture and relates it to user requirements for multi-tier servers, scale-out models, networking technology advances, and industry trends. Design decisions and challenges, the switch subsystem and input/output technology options, services that are currently supported by the architecture, and future enhancements and extensions are addressed.
Infection of Owl Monkeys (Aotus trivirgatus) and Cynomolgus Monkeys (Macaca fascicularist) with Hepatitis E Virus from Mexico (1992)

Owl and cynomolgus monkeys were inoculated with hepatitis E virus (HEV) to compare disease models and produce antibody and virus. By immune electron microscopy (IEM), all six owl monkeys were shown to have serologic responses manifested by unusually high levels of anti-HEV at 6 months, but only three developed hepatitis. Virus-related antigen in liver (HEV Ag) was detected by immunofluorescence microscopy of biopsies from two of four owl monkeys; one with HEV Ag also had HEV in acute-phase bile (detected by IEM) and feces (detected by infecting another owl monkey). In contrast, cynomolgus monkeys propagated HEV to higher levels and all five had hepatitis. Moderate-to-high levels of HEV Ag correlated with detectable HEV in bile for both species. Thus, the value of using HEV-infected cynomolgus was confirmed. Owl monkeys were shown to be HEV-susceptible and sources of high-level anti-HEV; Sustained anti-HEV in these monkeys may also be useful for understanding immune responses.
Differential, Dose Dependent Changes in Cognitive Performance Following Acute Administration of aGinkgo biloba/Panax ginsengCombination to Healthy Young Volunteers (2001)

We have previously shown differential cognitive improvements following single doses of Ginkgo biloba and of Ginseng. There is also evidence that chronic administration of a combination of standardised extracts of Ginkgo biloba and Panax ginseng may improve aspects of cognitive performance both in pathological populations and the healthy middle aged. No investigation has thus far looked either at the cognitive effects of single doses of such a combination, nor the effects of the combination on healthy young volunteers. The present study investigated whether acute administration of a combination of standardised extracts of Ginkgo biloba (GK501, Pharmaton SA) and Ginseng (G115, Pharmaton SA) had any consistent effect on mood and aspects of cognitive performance ("quality of memory", "secondary memory", "working memory", "speed of memory", "quality of attention" and "speed of attention") that can be derived by factor analysis of the cognitive drug research computerised assessment battery. The study followed a placebo-controlled, double blind, balanced, crossover design. Twenty healthy young adult volunteers received 320, 640, and 960 mg of the combination, and a matching placebo, in an order dictated by random allocation to a Latin square, and with a seven-day wash-out period between treatments. Following a baseline cognitive assessment, further test sessions took place 1, 2.5,4 and 6 h after the day's treatment. The most striking result was a dose-dependent improvement in performance on the "quality of memory" factor for the highest dose. Further analysis revealed that this effect was differentially targeted at the secondary memory rather than the working memory component. There was also a dose dependent decrement in performance of the "speed of attention" factor for both the 320 and 640 mg doses. These results are discussed in the context of previous findings within this series of studies.
Mouse opsin promoter-directed Cre recombinase expression in transgenic mice. (2006)

We have generated transgenic mice expressing Cre recombinase in rod photoreceptors. One transgenic mouse line was capable of carrying out efficient Cre-mediated recombination in rod photoreceptors. Another transgenic mouse line was capable of carrying out mosaic Cre-mediated recombination in rod photoreceptors and bipolar cells across the whole retina. These mice will be useful tools for Cre/lox-based gene activation and inactivation, as well as genetic mosaics, in rod photoreceptors and rod bipolar cells.
Laying the Rod to Rest: Narrative Strategies in Gisela and Bettina von Arnim's Fairy-Tale Novel Gritta (1997)

Fairy tales by German women authors follow two European traditions that set them apart from the Grimms’ Kinder- und Hausmarchen: first, they frequently emulate the moralizing tales of French and Enlightenment literature; and, second, they often present tales framed by other tales and narrative settings, as did the tale cycles in the pre-modern period such as the Thousand and One Nights and the Pentamarone. The fairy-tale novel by Bettina and Gisela von Arnim, Das Leben der Hochgräfin Gritta von Rattenzuhausbeiuns (The Life of the Countess Gritta von Ratsatourhouse, ca. 1843), is the best and most complicated example of the “Chinese box” narrative structure and imbedded social criticism in German women’s fairy tales. This novel deconstructs fairy-tale archetypes of female behavior by rewriting the roles of stepmother, wise women, and nice (brav) little girls. The interlocking narratives criticize patriarchal notions of punishment, particularly punishment of female independence and mobility.
Handwritten month word recognition on Brazilian bank cheques (2002)

This paper describes an off-line system under development to process unconstrained handwritten dates on Brazilian bank cheques in an omni-writer context. We show here some improvements on our previous work on isolated month word recognition using hidden Markov models (HMM). After preprocessing, a word image is explicitly segmented into characters or pseudo-characters and represented by two feature sequences of equal length, which are combined using HMM. The word models are generated from the concatenation of appropriate character models. In addition to the small date database, we also make use of the legal amount database to increase the frequency of characters in the training and the validation sets. Although this study deals with a limited lexicon, the many similarities among the word classes can affect the performance of the recognition. Experiments show an increase in the average recognition rate from 84% to 91%. Finally, we present our perspectives of future work.
Efficacy Trial of a DNA/rAd5 HIV-1 Preventive Vaccine (2013)

The DNA/rAd5 vaccine regimen did not reduce either the rate of HIV-1 acquisition or the viral-load set point in the population studied. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT00865566.).
Learning and Leveraging the Relationship between Architecture-Level Measurements and Individual User Satisfaction (2008)

The ultimate goal of computer design is to satisfy the end-user. In particular computing domains, such as interactive applications, there exists a variation in user expectations and user satisfaction relative to the performance of existing computer systems. In this work, we leverage this variation to develop more efficient architectures that are customized to end-users. We first investigate the relationship between microarchitectural parameters and user satisfaction. Specifically, we analyze the relationship between hardware performance counter (HPC) readings and individual satisfaction levels reported by users for representative applications. Our results show that the satisfaction of the user is strongly correlated to the performance of the underlying hardware. More importantly, the results show that user satisfaction is highly user-dependent. To take advantage of these observations, we develop a framework called Individualized Dynamic Voltage and Frequency Scaling (iDVFS). We study a group of users to characterize the relationship between the HPCs and individual user satisfaction levels. Based on this analysis, we use artificial neural networks to model the function from HPCs to user satisfaction for individual users. This model is then used online to predict user satisfaction and set the frequency level accordingly. A second set of user studies demonstrates that iDVFS reduces the CPU power consumption by over 25% in representative applications as compared to the Windows XP DVFS algorithm.
Agonistic 4-1bb antibodies in combination with inhibitory antibodies against CTLA-4, PD-L1 or LAG-3 ACT on CD8+ T cells in the tumor microenvironment and synergize to promote regression of established tumors (2014)

Meeting abstracts Tumors can be placed into two categories: those that are T cell-inflamed and those that are not, based on specific chemokine and type I interferon gene expression signatures and CD8+ tumor infiltrating T cells (TIL). That these immune-inflamed tumors are not destroyed by the CD8+
Determination of the extent of DNA bending by an adenine-thymine tract (1990)

We determined the magnitude of the bend induced in DNA by an adenine-thymine tract by measuring the rate of cyclization of DNA oligonucleotides containing phased A tracts. A series of linear multimers with 2-bp single-stranded ends, in which the (A.T)6 tracts are separated by CG2-3C sequences and are positioned 10 and 11 bp apart alternately, were prepared from 21 bp long synthetic duplexed deoxyoligonucleotides. The cyclization rates of the multimers (105-210 bp) and the bimolecular association rate of the 84 bp long multimer were measured in the presence of DNA ligase. From the rate constants of the cyclization and bimolecular association reactions, ring closure probabilities were obtained for the multimers. The systematically bent molecules were simulated by Monte Carlo methods, and the ring closure probabilities were calculated for a given set of junction bend angles. By comparing the calculated values of ring closure probabilities to experimental values and adjusting the junction bend angles to fit experimental values, the extent of bending at the junctions (or the extent of bending for an adenine tract) was determined. We conclude that an A6 tract bends the DNA helix by 17-21 degrees.
Synthetic Retinoid Am80 Reduces Scavenger Receptor Expression and Atherosclerosis in Mice by Inhibiting IL-6 (2006)

Am80 suppresses scavenger receptor expression and macrophage foam cell formation in vitro and prevents atherogenesis in apoE-deficient mice in vivo. This suggests Am80 is a novel candidate agent that could be highly useful in the prevention and treatment of atherosclerosis.
Drag - Bit Model Including Wear (1994)

Abstract The model presented in this paper is a new approach to predicting the performance of full-hole and core drag bits. The model is based on theoretical considerations of single-cutter rock interaction, lithology coefficients and bit wear. Several new modeling features are introduced, these include "equivalent bit radius", "dynamic cutter action", "lithology coefficients" and "cutter wear". The model is applicable to all types of drag bits (Natural Diamond Bits (NDB), Polycrystalline Diamond Compact Bits (PDC) and any Geoset Bits) with correct cutter geometrical description. The model is useful for pre-planning, day to day and post drilling analysis, as well as drilling optimization. Application of the model to evaluate drag-bit performance has shown good results in several lab and field cases. The advantages of this model include, optimization of operating parameters, optimization of bit parameters and support of a total drilling system for penetration rate, solids control and hydraulics optimization. In addition, use of the model is simple and straight forward, data requirements are standard and readily available. Lithology coefficients can be obtained from lab data or one set of drill-off and/or bit performance test in the field. Penetration rates can be predicted by the model for different lithologiεs using rock strengths obtained from offset drilling or log data. In other words, the model will predict penetration rate for any set of operating conditions, formation description and bit parameters.
Smart structures for sensing environmental pollution (1999)

We present a novel composite sensing agent consisting of calix[4]resorcinarene (C[4]RA) and the conducting polyorthomethoxyaniline (POMA) and propose different sensing mechanisms that can take advantage of its nanoporosity and unique complexation reactions. The two main purposes of combining the materials are, to improve the deposition of the materials as Langmuir-Blodgett (LB) films and to create a nanoporous material that improves on the absorbtion / desorbtion behaviour of the films giving higher gas diffusion coefficients. LB films offer the highest control of film properties in comparison to alternative deposition methods and the inclusion of flexible calixarene in the polymer structure offers enhanced response and recovery times in comparison to straight chain molecules than steric acid. Further effects such as conductivity increases of the material of up to two orders of magnitude upon exposure to saturated vapours are also described. The results of the present studies are encouraging and promise potential for extended studies with alternative composites utilising different electroactive conjugated polymers and varying crown size calixarenes, but using the same deposition method.
Isoprenoid Biosynthesis. Metabolite Profiling of Peppermint Oil Gland Secretory Cells and Application to Herbicide Target Analysis (2001)

Two independent pathways operate in plants for the synthesis of isopentenyl diphosphate and dimethylallyl diphosphate, the central intermediates in the biosynthesis of all isoprenoids. The mevalonate pathway is present in the cytosol, whereas the recently discovered mevalonate-independent pathway is localized to plastids. We have used isolated peppermint (Mentha piperita) oil gland secretory cells as an experimental model system to study the effects of the herbicides fosmidomycin, phosphonothrixin, methyl viologen, benzyl viologen, clomazone, 2-(dimethylamino)ethyl diphosphate, alendronate, and pamidronate on the pools of metabolites related to monoterpene biosynthesis via the mevalonate-independent pathway. A newly developed isolation protocol for polar metabolites together with an improved separation and detection method based on liquid chromatography-mass spectrometry have allowed assessment of the enzyme targets for a number of these herbicides.