gebhart/patrepeval huggingface dataset:
Androgen Abuse by Athletes (1988)

ANDROGEN abuse by athletes constitutes only a portion of the problem of androgen misuse by the general population (1) and only a minor aspect of the doping of athletes with drugs presumed to enhance athletic ability (2, 3). Indeed, of the drugs banned by the International Olympic Committee, steroids account only for about 15% (4). This particular form of drug abuse stems from the convergence of several separate misconceptions. The first was the recognition that the administration of androgens to hypogonadal males causes an increase in nitrogen retention and an increase in muscle mass and lean body weight (5). It followed that the differences in muscle mass between men and women are largely due to differences in testosterone levels, and it was assumed that the administration of androgens in supraphysiological amounts to normal men would do even more than the normal amount. The second misconception was that the anabolic (muscle promoting) and androgenic (virilizing) actions of the hormone are exerted by different mechanisms and that pure anabolic agents could be devised that would be devoid of or have minimal androgenic effects (6, 7). In fact, androgenic and anabolic effects are not due to different actions of the hormone but result from interaction of the hormone with the same receptor molecule in different tissues (1). In men with normal levels of plasma androgens the androgen receptor in most tissues appears either to be saturated or downregulated. Thus, it has not been possible to separate the two types of actions at the pharmacological or physiological levels, and in normal men any anabolic actions obtained from exogenous androgens are inevitably limited in scope. The third misconception, at least in the United States, stemmed from international competitiveness in sports. According to a widely accepted account, John B. Ziegler, a physician for the US weight lifting team, was told by a Russian team physician at the 1954 world weight lifting championship in Vienna that some members of the Russian team used androgens (8–10). Ziegler assumed that androgens would enhance athletic performance, and he began to experiment in American weight lifters with the various agents that had been developed as candidates for pure anabolic steroids (8). He subsequently concluded that the effects of androgens are purely psychological (9, 10).
Outwitting the Blood-Brain Barrier for Therapeutic Purposes: Osmotic Opening and Other Means (1998)

Improving delivery of agents to the brain will play a major role in the therapeutic outcome of brain neoplasms. As techniques for gene therapy are advanced, manipulation of the BBB also may be important in the treatment of central nervous system genetic disorders.
Cross-Protection against Marburg Virus Strains by Using a Live, Attenuated Recombinant Vaccine (2006)

Marburg virus (MARV) has been associated with sporadic episodes of hemorrhagic fever, including a recent highly publicized outbreak in Angola that produced severe disease and significant mortality in infected patients. MARV is also considered to have potential as a biological weapon. Recently, we reported the development of a promising attenuated, replication-competent vaccine against MARV based on recombinant vesicular stomatitis virus (VSV) expressing the glycoprotein of the Musoke strain of MARV (VSVDeltaG/MARVGP-Musoke). We used this vaccine to demonstrate complete protection of cynomolgus monkeys against a homologous MARV challenge. While these results are highly encouraging, an effective vaccine would need to confer protection against all relevant strains of MARV. Here, we evaluated the protective efficacy of the VSVDeltaG/MARVGP-Musoke vaccine against two heterologous MARV strains, the seemingly more pathogenic Angola strain and the more distantly related Ravn strain. In this study, seven cynomolgus monkeys were vaccinated with the VSVDeltaG/MARVGP-Musoke vector. Three of these animals were challenged with the Angola strain, three with the Ravn strain, and a single animal with the Musoke strain of MARV. Two animals served as controls and were each injected with a nonspecific VSV vector; these controls were challenged with the Angola and Ravn strains, respectively. Both controls succumbed to challenge by day 8. However, none of the specifically vaccinated animals showed any evidence of illness either from the vaccination or from the MARV challenges and all of these animals survived. These data suggest that the VSVDeltaG/MARVGP-Musoke vaccine should be sufficient to protect against all known MARV strains.
Associations and Interactions between Bare Lymphocyte Syndrome Factors (2000)

The bare lymphocyte syndrome, a severe combined immunodeficiency due to loss of major histocompatibility complex (MHC) class II gene expression, is caused by inherited mutations in the genes encoding the heterotrimeric transcription factor RFX (RFX-B, RFX5, and RFXAP) and the class II transactivator CIITA. Mutagenesis of the RFX genes was performed, and the properties of the proteins were analyzed with regard to transactivation, DNA binding, and protein-protein interactions. The results identified specific domains within each of the three RFX subunits that were necessary for RFX complex formation, including the ankyrin repeats of RFX-B. DNA binding was dependent on RFX complex formation, and transactivation was dependent on a region of RFX5. RFX5 was found to interact with CIITA, and this interaction was dependent on a proline-rich domain within RFX5. Thus, these studies have defined the protein domains required for the functional regulation of MHC class II genes.
Bortezomib Mediates Antiangiogenesis in Multiple Myeloma via Direct and Indirect Effects on Endothelial Cells (2006)

Bone marrow angiogenesis plays an important role in the pathogenesis and progression in multiple myeloma. Recent studies have shown that proteasome inhibitor bortezomib (Velcade, formerly PS-341) can overcome conventional drug resistance in vitro and in vivo; however, its antiangiogenic activity in the bone marrow milieu has not yet been defined. In the present study, we examined the effects of bortezomib on the angiogenic phenotype of multiple myeloma patient-derived endothelial cells (MMEC). At clinically achievable concentrations, bortezomib inhibited the proliferation of MMECs and human umbilical vein endothelial cells in a dose-dependent and time-dependent manner. In functional assays of angiogenesis, including chemotaxis, adhesion to fibronectin, capillary formation on Matrigel, and chick embryo chorioallantoic membrane assay, bortezomib induced a dose-dependent inhibition of angiogenesis. Importantly, binding of MM.1S cells to MMECs triggered multiple myeloma cell proliferation, which was also abrogated by bortezomib in a dose-dependent fashion. Bortezomib triggered a dose-dependent inhibition of vascular endothelial growth factor (VEGF) and interleukin-6 (IL-6) secretion by the MMECs, and reverse transcriptase-PCR confirmed drug-related down-regulation of VEGF, IL-6, insulin-like growth factor-I, Angiopoietin 1 (Ang1), and Ang2 transcription. These data, therefore, delineate the mechanisms of the antiangiogenic effects of bortezomib on multiple myeloma cells in the bone marrow milieu.
SAPAPs (1997)

PSD-95/SAP90 is a member of membrane-associated guanylate kinases localized at postsynaptic density (PSD) in neuronal cells. Membrane-associated guanylate kinases are a family of signaling molecules expressed at various submembrane domains which have the PDZ (DHR) domains, the SH3 domain, and the guanylate kinase domain. PSD-95/SAP90 interacts with N-methyl-D-aspartate receptors 2A/B, Shaker-type potassium channels, and brain nitric oxide synthase through the PDZ (DHR) domains and clusters these molecules at synaptic junctions. However, neither the function of the SH3 domain or the guanylate kinase domain of PSD-95/SAP90, nor the protein interacting with these domains has been identified. We have isolated here a novel protein family consisting of at least four members which specifically interact with PSD-95/SAP90 and its related proteins through the guanylate kinase domain, and named these proteins SAPAPs (SAP90/PSD-95-Associated Proteins). SAPAPs are specifically expressed in neuronal cells and enriched in the PSD fraction. SAPAPs induce the enrichment of PSD-95/SAP90 to the plasma membrane in transfected cells. Thus, SAPAPs may have a potential activity to maintain the structure of PSD by concentrating its components to the membrane area.
Event-based Priming (2004)

Several recent articles have emphasized event representations and their role in language processing. For example, Vu et al. (2003) used subject nouns such as astronomer versus director to promote a situation model that led to disambiguating the meaning of a sentence-final word such as star. They found that their manipulation was sufficient to activate selectively the dominant or subordinate meaning of the ambiguous noun. Ferretti, McRae, and Hatherell (2001) used short stimulus onset asynchrony priming to provide evidence that verbs denoting events quickly activate knowledge of typical aspects of those events (verbs primed typical agents, patients, and instruments). McRae et al. (2004) found that nouns denoting typical aspects of events activate verbs, thus suggesting that event knowledge is computed quickly via means other than
A human parvovirus, adeno-associated virus, as a eucaryotic vector: transient expression and encapsidation of the procaryotic gene for chloramphenicol acetyltransferase. (1984)

We have used the defective human parvovirus adeno-associated virus (AAV) as a novel eucaryotic vector (parvector) for the expression of a foreign gene in human cells. The recombinant, pAV2, contains the AAV genome in a pBR322-derived bacterial plasmid. When pAV2 is transfected into human cells together with helper adenovirus particles, the AAV genome is rescued from the recombinant plasmid and replicated to produce infectious AAV particles at high efficiency. To create a vector, we inserted a procaryotic sequence coding for chloramphenicol acetyltransferase (CAT) into derivatives of pAV2 following either of the AAV promoters p40 (pAVHiCAT) and p19 (pAVBcCAT). When transfected into human 293 cells or HeLa cells, pAVHiCAT expressed CAT activity in the absence of adenovirus. In the presence of adenovirus, this vector produced increased amounts of CAT activity and the recombinant AAV-CAT genome was replicated. In 293 cells, pAVBcCAT expressed a similar amount of CAT activity in the absence or presence of adenovirus and the recombinant AAV-CAT genome was not replicated. In HeLa cells, pAVBcCAT expressed low levels of CAT activity, but this level was elevated by coinfection with adenovirus particles or by cotransfection with a plasmid which expressed the adenovirus early region 1A (E1A) product. The E1A product is a transcriptional activator and is expressed in 293 cells. Thus, expression from two AAV promoters is differentially regulated: expression from p19 is increased by E1A, whereas p40 yields high levels of constitutive expression in the absence of E1A. Both AAV vectors were packaged into AAV particles by complementation with wild-type AAV and yielded CAT activity when subsequently infected into cells in the presence of adenovirus.
Ionizing radiation and UV induction of p53 protein by different pathways in ataxia-telangiectasia cells. (1993)

Cell cycle anomalies have been described in ataxia-telangiectasia cells after exposure to ionizing radiation. A recent report demonstrates that cells from these patients lack the ionizing radiation-induced increase in p53 protein seen in controls. We report here that an ionizing radiation-induced p53 response is reduced and/or delayed in cells from four ataxia-telangiectasia complementation groups. On the other hand, p53 induction is normal in all A-T complementation groups after exposure to UV-B light, an agent to which these cells are not hypersensitive. Specific inhibitors of protein kinase C and serine/threonine phosphatases prevented the radiation induction of p53 protein. Agents that produced double-strand breaks in DNA and/or inhibition of transcription caused an induction of p53 in the absence of radiation in control cells but not in ataxia-telangiectasia, but inhibitors of cell cycle progression such as mimosine and aphidicolin led to an increase in p53 in both cell types in the absence of radiation. These results suggest that there is more than one signal transduction pathway responsible for activation of p53, one of which is less efficient in ataxia-telangiectasia cells.
Receptor-Misrouting: An Unexpectedly Prevalent and Rescuable Etiology in Gonadotropin-Releasing Hormone Receptor-Mediated Hypogonadotropic Hypogonadism (2002)

Fourteen mutations (13 missense and 1 truncation) of the GnRH receptor (GnRHR) have been identified in patients with hypogonadotropic hypogonadism (HH). We have previously shown that five of the missense mutations can be rescued with a GnRH peptidomimetic antagonist that acts as folding template, stabilizing (otherwise) misfolded GnRHR mutants and thereby restoring function. We now report that this approach rescues 11 of 13 of these GnRHR missense mutants. These data indicate the surprisingly general nature of this approach, an observation that presents therapeutic opportunities for HH and other disorders resulting from protein misfolding. A classification system for GnRHR mutants is proposed.
Issues in Discretionary Access Control (1985)

This paper discusses the types of mechanisms that can be used to implement Discretionary Access Control (DAC). It also covers the access types that can be controlled by a DAC mechanism. and includes a brief discussion of related topics including protected subsystems; administering, auditing, and verifying DAC; and DAC implemented as an add-on to an operating system. Finally this paper discusses how the DAC information presented in this paper will be used by the Department of Defense Computer Security Center in the preparation of a DAC Guideline to aid system designers and developers in their selection of DAC mechanisms.
Complex regulation of collagen gene expression in cultured bovine aortic smooth muscle cells. (1986)

Cultured bovine aortic smooth muscle cells display an increase in production of type I and type III collagen as a function of the number of days in second passage (Beldekas, J. C., Gerstenfeld, L. C., Sonenshein, G. E., and Franzblau, C. (1982) J. Biol. Chem. 257, 12552-12556). In this study, we report that the regulation of these events is highly complex and relates to the growth state of the cells. Cultures, seeded at 1.5 X 10(6) cells/75-cm2 flask, produced very little collagenous protein early when the cells were proliferating rapidly. As they approached confluence at day 6, collagen synthesis began to increase. Maximal collagen synthesis was observed at day 14. In contrast, the levels of the mRNAs for type I and type III collagen increased only up to the 10th day and thereafter decreased. Cell-free translation analyses indicated that the translational activity of the collagen mRNAs was increasing over the time course. These results suggest that both translational and pretranslational sites are involved in the control of collagen production by aortic smooth muscle cells, and that collagen synthesis is inversely related to the proliferative state of the cells in culture.
CD26/Dipeptidyl-Peptidase IV Down-Regulates the Eosinophil Chemotactic Potency, But Not the Anti-HIV Activity of Human Eotaxin by Affecting Its Interaction with CC Chemokine Receptor 3 (1999)

Chemokines attract and activate distinct sets of leukocytes. The CC chemokine eotaxin has been characterized as an important mediator in allergic reactions because it selectively attracts eosinophils, Th2 lymphocytes, and basophils. Human eotaxin has a penultimate proline, indicating that it might be a substrate for dipeptidyl-peptidase IV (CD26/DPP IV). In this study we demonstrate that eotaxin is efficiently cleaved by CD26/DPP IV and that the NH2-terminal truncation affects its biological activity. CD26/DPP IV-truncated eotaxin(3-74) showed reduced chemotactic activity for eosinophils and impaired binding and signaling properties through the CC chemokine receptor 3. Moreover, eotaxin(3-74) desensitized calcium signaling and inhibited chemotaxis toward intact eotaxin. In addition, HIV-2 infection of CC chemokine receptor 3-transfected cells was inhibited to a similar extent by eotaxin and eotaxin(3-74). Thus, CD26/DPP IV differently regulates the chemotactic and antiviral potencies of eotaxin by the removal of two NH2-terminal residues. This physiological processing may be an important down-regulatory mechanism, limiting eotaxin-mediated inflammatory responses.
Small Animal Models of Kidney Disease: A Review (2008)

Animal models of renal disease have provided valuable insights into the pathogenesis of acute and chronic kidney disease. Extension of these models to the mouse has become an increasingly important with the development of gene knockout and transgenic animals. In this review we discuss a range of models that can be used to mimic the mechanisms of human renal disease. While not perfect, the careful and ethical use of these models offers the opportunity to examine individual mechanisms in an accelerated time frame.
Two-Dimensional Separation of Membrane Proteins by 16-BAC-SDS-PAGE (2009)

Defining membrane proteomes is fundamental to our understanding of many physiological and pathophysiological processes. Their separation and identification is hence a key issue in basic and biomedical research. Due to their hydrophobic character, few high-resolution techniques for separation are available for qualitative and quantitative approaches. For gel-based methods, the two-dimensional 16-BAC/SDS-PAGE is the method of choice. This technique separates proteins in the first dimension using an acidic buffer system and the cationic detergent benzyldimethyl-n-hexadecylammonium chloride (16-BAC) and in the second dimension by SDS-PAGE. Here, we describe a detailed protocol for the separation of proteins by 16-BAC/SDS-PAGE.
Principles of morality (2006)

General preface Editorial notes Introduction Question 18. Good and moral evil in human acts in general Question 19. Moral good and evil in the will's inner activity Question 20. Moral good and evil in outward acts Question 21. Corollaries to moral good and evil in human acts Appendices Glossary Index.
Hybrid high refractive index polymer coatings (2005)

Thermally curable hybrid high refractive index polymer solutions have been developed. These solutions are stable up to 6 months under room temperature storage conditions and can be easily spin-coated onto a desired substrate. When cured at elevated temperature, the hybrid polymer coating decomposes to form a metal oxide-rich film that has a high refractive index. The resulting films have refractive indices higher than 1.90 in the entire visible region and achieve film thicknesses of 300-900 nm depending on the level of metal oxide loading, cure temperature being used, and number of coatings. The formed films show greater than 90% internal transmission in the visible wavelength (400-700 nm). These hybrid high refractive index films are mechanically robust, are stable upon exposure to both heat and UV radiation, and are currently being investigated for microlithographic patterning potential.
Preclinical PET imaging of bispecific antibody ERY974 targeting CD3 and glypican 3 reveals that tumor uptake correlates to T cell infiltrate (2020)

<sup>[89Zr]</sup>Zr-N-suc-Df-ERY974 can potentially be used to study ERY974 biodistribution in patients to support drug development.
A multiplex assay for the simultaneous detection of antibodies against 15 Plasmodium falciparum and Anopheles gambiae saliva antigens (2010)

The multiplex assay developed here provides a useful tool to evaluate immune responses to multiple Ags in large populations, even when only small amounts of serum are available, or Ab titres are low, as in case of travellers. Finally, the relationship of Ab responses with malaria endemicity levels provides a way to monitor exposure in differentially exposed autochthonous individuals from various endemicity areas, as well as in travellers who are not immune, thus indirectly assessing the parasite transmission and malaria risk in the new eradication era.
Pleckstrin homology (PH) like domains – versatile modules in protein–protein interaction platforms (2012)

The initial reports on pleckstrin homology (PH) domains almost 20 years ago described them as sequence feature of proteins involved in signal transduction processes. Investigated at first along the phospholipid binding properties of a small subset of PH representatives, the PH fold turned out to appear as mediator of phosphotyrosine and polyproline peptide binding to other signaling proteins. While phospholipid binding now seems rather the exception among PH-like domains, protein-protein interactions established as more and more important feature of these modules. In this review we focus on the PH superfold as a versatile protein-protein interaction platform and its three-dimensional integration in an increasing number of available multidomain structures.
Imidazoline scaffold in medicinal chemistry: a patent review (2012–2015) (2016)

2-Substituted imidazolines can exist in multiple tautomeric forms. The implication is that imidazolines and their imidazolidine tautomers cannot be regarded as isofunctional structures and the term 'imidazoline scaffold' should be treated with caution. Nevertheless, for medicinal chemists the progress made in development of both the imidazoline- and imidazolidine-containing agents useful for the treatment of neurodegenerative, inflammatory, autoimmune, cancer, and infectious diseases is of the utmost importance.
Biodiesel production—current state of the art and challenges (2008)

Biodiesel is a clean-burning fuel produced from grease, vegetable oils, or animal fats. Biodiesel is produced by transesterification of oils with short-chain alcohols or by the esterification of fatty acids. The transesterification reaction consists of transforming triglycerides into fatty acid alkyl esters, in the presence of an alcohol, such as methanol or ethanol, and a catalyst, such as an alkali or acid, with glycerol as a byproduct. Because of diminishing petroleum reserves and the deleterious environmental consequences of exhaust gases from petroleum diesel, biodiesel has attracted attention during the past few years as a renewable and environmentally friendly fuel. Since biodiesel is made entirely from vegetable oil or animal fats, it is renewable and biodegradable. The majority of biodiesel today is produced by alkali-catalyzed transesterification with methanol, which results in a relatively short reaction time. However, the vegetable oil and alcohol must be substantially anhydrous and have a low free fatty acid content, because the presence of water or free fatty acid or both promotes soap formation. In this article, we examine different biodiesel sources (edible and nonedible), virgin oil versus waste oil, algae-based biodiesel that is gaining increasing importance, role of different catalysts including enzyme catalysts, and the current state-of-the-art in biodiesel production.