gebhart/patrepeval huggingface dataset:
Hormonal regulation of prostate‐specific antigen (PSA) glycoprotein in the human prostatic adenocarcinoma cell line, LNCaP (1992)

Prostate-specific antigen (PSA) has emerged as the most useful marker for management of patients with prostate cancer. The regulation of this glycoprotein in vivo has important clinical implications. Indirect evidence indicates that the PSA glycoprotein might be regulated by androgens, and previous studies in this laboratory have demonstrated that PSA mRNA is upregulated by androgens. The current work reports a detailed study of PSA glycoprotein expression as influenced by steroid hormones in a human prostatic adenocarcinoma cell line, LNCaP. First, we have examined the steroid binding specificity of the androgen receptor in this cell line. In comparison with wild-type rat androgen receptor in prostate, the receptor in LNCaP cells has altered affinity for a number of steroids or analogs such as progesterone (R5020), antiprogesterone (RU486), two antiandrogens (cyperoterone acetate and hydroxyflutamide), and an androgen metabolite (epitestosterone). However, its affinity for androgens (mibolerone, dihydrotestosterone, and testosterone) is not changed. The receptor does not bind to the synthetic glucocorticoids (triaminolone acetonide and dexamethasone) nor to a synthetic estrogen DES (diethylstilbestrol). The change of the steroid binding specificity of the receptor is correlated with a single mutation (A----G at nucleotide #876 relative to the initiation codon) of the steroid binding domain of the receptor. The mutation and alteration of steroid-binding specificity of the androgen receptor is also correlated with PSA glycoprotein expression affected by different ligands tested. We have demonstrated that the PSA glycoprotein is upregulated by androgens and is affected by neither epidermal growth factor nor basic fibroblast growth factor. Moreover, PSA glycoprotein could be induced by R5020, estradiol, and epitestosterone; but neither glucocorticoids nor DES had any effect on PSA induction. Interestingly, although the antiandrogen, cyperotone acetate, had the ability to induce PSA, both RU486 and hydroxyflutamide could block androgen and progesterone induction of PSA glycoprotein. Therefore, we conclude that the PSA glycoprotein expression is influenced predominantly by androgens via its receptor, and the mutation of the receptor can affect the expression of this cellular gene by the steroids other than androgens.
Going against the Grain (2007)

Overturning the received wisdom of a field takes not just strong evidence, but a strong personality. For one reproductive biologist, only time will tell whether such challenges are worth the risks in today's pressurized research climate.
<title>Comparative performance of watermarking schemes using M-ary modulation with binary schemes employing error correction coding</title> (2001)

A common application of digital watermarking is to encode a small packet of information in an image, such as some form of identification that can be represented as a bit string. One class of digital watermarking techniques employs spread spectrum like methods where each bit is redundantly encoded throughout the image in order to mitigate bit errors. We typically require that all bits be recovered with high reliability to effectively read the watermark. In many watermarking applications, however, straightforward application of spread spectrum techniques is not enough for reliable watermark recovery. We therefore resort to additional techniques, such as error correction coding. As proposed by M. Kutter 1, M-ary modulation is one such technique for decreasing the probability of error in watermark recovery. It1 was shown that M-ary modulation techniques could provide performance improvement over binary modulation, but direct comparisons to systems using error correction codes were not made. In this paper we examine the comparative performance of watermarking systems using M-ary modulation and watermarking systems using binary modulation combined with various forms of error correction. We do so in a framework that addresses both computational complexity and performance issues.
Exenatide Improves Glycemic Control and Reduces Body Weight in Subjects with Type 2 Diabetes: A Dose-Ranging Study (2005)

Exenatide dose-dependently improved glycemic control and reduced body weight over 28 days in patients with type 2 diabetes treated with diet/exercise or metformin.
Transposon Tagging and Molecular Analysis of the Maize Regulatory Locus opaque-2 (1987)

Genetic analyses suggested that the opaque-2 (o2) locus in maize acts as a positive, transacting, transcriptional activator of the zein seed storage-protein genes. Because isolation of the gene is requisite to understanding the molecular details of this regulation, transposon mutagenesis with the transposable element suppressor-mutator (Spm) was carried out, and three mutable o2 alleles were obtained. One of these alleles contained an 8.3-kilobase autonomous Spm, another a 6.8-kilobase nonautonomous Spm, and the third an unidentified transposon that is unrelated to Spm. A DNA sequence flanking the autonomous Spm insertion was verified to be o2-specific and provided a probe to clone a wild-type allele. Northern blots indicated that the gene is expressed in wild-type endosperm but not in leaf tissues or in endosperms homozygous for a mutant allele of the O2 gene. A transcript was detected in endosperms homozygous for mutations at opaque-7 and floury-2, an indication that O2 expression is independent of these two other putative regulators of zein synthesis.
Glutathione biosynthesis in the isolated perfused rat lung: utilization of extracellular glutathione (1984)

The isolated perfused rat lung catalyzed the biosynthesis of GSH when the sulfur amino acids cysteine or N-acetylcysteine, but not methionine, were supplied in the perfusion medium. The lung also had the capacity to utilize extracellular GSH for this purpose. Replenishment of intracellular GSH in perfused lungs from diethylmaleate-treated rats was pronounced even at 25 microM GSH in the perfusion medium. The utilization of extracellular GSH is probably primarily through extracellular break-down and resynthesis rather than direct uptake as indicated by the inhibitory effect of the gamma-glutamylcysteine synthetase inhibitor, buthionine sulfoximine and the gamma-glutamyl transferase inhibitor, anthglutin. The results indicate that the lung in addition to the kidney may utilize circulating plasma GSH.
Using objects and patterns to implement domain ontologies (2002)

Ontologies are becoming an important mechanism to build information systems. Nevertheless, there is still no systematic approach to support the design of such systems using tools that are common to information systems developers. In this paper, we propose an approach for deriving object frameworks from domain ontologies and then we show the application of this approach in the software process domain.
On the in vivo action of erythropoietin: a quantitative analysis (1972)

The composite response of the erythron to exogenous erythropoietin has been studied in normal, splenectomized, and polycythemic mice. After stimulation the normal animal doubled its marrow nucleated red cells by the 3rd day with little further change by the 5th. Nucleated red cells within the spleen began to increase sharply on the 2nd day and, by the 5th, exceeded those in the marrow. The total nucleated erythroid response represented a fourfold increase. Reticulocytes lagged behind the expansion of the nucleated red cell mass, but by the 5th day the original ratio was re-established. Hemoglobin synthesis was increased, but the ratio of hemoglobin synthesized in nucleated red cells and reticulocytes was basically unchanged. Early displacement of marrow reticulocytes into circulation and the production of a larger red cell also occurred. No evidence of a change in the number of erythroid mitoses was found; only a slight decrease in the average cell cycle time was demonstrated. Thus, whereas erythropoietin stimulation induced several changes in erythropoiesis, the increased number of cells entering into the maturing pool appeared to be of greatest quantitative significance.Splenectomy reduced the proliferative response of the erythron over 5 days stimulation to three-fourths that found in the normal animal. This difference, also reflected in a proportionately lower reticulocyte response and increment in circulating red cell mass, suggests that erythropoiesis within the mouse marrow is spatially or otherwise restricted and that the spleen provided a supplemental area of erythroid expansion.
Human Skin Culture as an Ex Vivo Model for Assessing the Fibrotic Effects of Insulin-Like Growth Factor Binding Proteins (2008)

Systemic sclerosis (SSc) is a connective tissue disease of unknown etiology. A hallmark of SSc is fibrosis of the skin and internal organs. We recently demonstrated increased expression of IGFBP-3 and IGFBP-5 in primary cultures of fibroblasts from the skin of patients with SSc. In vitro, IGFBP-3 and IGFBP-5 induced a fibrotic phenotype and IGFBP-5 triggered dermal fibrosis in mice. To assess the ability of IGFBPs to trigger fibrosis, we used an ex vivo human skin organ culture model. Our findings demonstrate that IGFBP-3 and IGFBP-5, but not IGFBP-4, increase dermal and collagen bundle thickness in human skin explants, resulting in substantial dermal fibrosis and thickening. These fibrotic effects were sustained for at least two weeks. Our findings demonstrate that human skin ex vivo is an appropriate model to assess the effects of fibrosis-inducing factors such as IGFBPs, and for evaluating the efficacy of inhibitors/therapies to halt the progression of fibrosis and potentially reverse it.
Enhanced activation of human T cells via avipox vector-mediated hyperexpression of a triad of costimulatory molecules in human dendritic cells. (2001)

T-cell activation usually requires at least two signals. The first signal is antigen-specific, and the second signal(s) involves the interaction of a T-cell costimulatory molecule(s) on the antigen-presenting cell (APC) with its ligand on the T cell. Dendritic cells (DCs) are the most potent APCs, attributable, in part, to their expression of several T-cell costimulatory molecules. Human DCs generated in vitro, however, will vary in methods of generation and maturation and in terms of expression of different phenotypic markers-including costimulatory molecules-among different donors. We report here that a recombinant avipox (fowlpox, rF) vector has been constructed that can efficiently express the transgenes for three human T-cell costimulatory molecules (B7-1, ICAM-1, and LFA-3) as a result of individual early avipox promoters driving the expression of each transgene. This triad of costimulatory molecules (designated TRICOM) was selected because each has an individual ligand on T cells and each has been shown previously to prime a unique signaling pathway in T cells. We report here that rF-TRICOM can efficiently infect human DCs of different states of maturity and hyperexpress each of the three costimulatory molecules on the DC surface without affecting other DC phenotypic markers. Infection of influenza or human papilloma virus 9-mer peptide-pulsed DCs from different individuals, or at different stages of maturity with rF-TRICOM, resulted in enhanced activation of T cells from peripheral blood mononuclear cells of autologous donors after 24 h of incubation with DCS: This enhanced activation was analyzed by both titrating the peptide and differing the DC:effector cell ratios. No effect was observed using the control wild-type avipox vector. No increase in apoptosis was observed in T cells hyperstimulated with the TRICOM vector, and no decrease in interleukin-12 production was seen in lipopolysaccharide-stimulated DCs infected with rF-TRICOM. Antibody-blocking experiments demonstrated that enhanced T-cell activation by TRICOM was attributed to each of the three costimulatory molecules. Peptide-pulsed, rF-TRICOM-infected DCs were also shown to be more effective than peptide-pulsed DCs in activating T cells to 9-mer peptides derived from two relatively weak "self" immunogens, i.e., human prostate-specific antigen and human carcinoembryonic antigen. These studies thus demonstrate for the first time that a vector that can simultaneously hyperexpress three costimulatory molecules can be used to efficiently infect human DCs, leading to enhanced peptide-specific T-cell activation. The use of this approach for in vitro studies and clinical applications in immunotherapy is discussed.
Shortened Modified Look-Locker Inversion recovery (ShMOLLI) for clinical myocardial T1-mapping at 1.5 and 3 T within a 9 heartbeat breathhold (2010)

ShMOLLI is an efficient method that generates immediate, high-resolution myocardial T1-maps in a short breath-hold with high precision. This technique provides a valuable clinically applicable tool for myocardial tissue characterisation.
Protein database searches for multiple alignments. (1990)

Protein database searches frequently can reveal biologically significant sequence relationships useful in understanding structure and function. Weak but meaningful sequence patterns can be obscured, however, by other similarities due only to chance. By searching a database for multiple as opposed to pairwise alignments, distant relationships are much more easily distinguished from background noise. Recent statistical results permit the power of this approach to be analyzed. Given a typical query sequence, an algorithm described here permits the current protein database to be searched for three-sequence alignments in less than 4 min. Such searches have revealed a variety of subtle relationships that pairwise search methods would be unable to detect.
Virtual Sound Sources in the Total Surround Sound System (1995)

The Total Surround Sound (TSS) System* has been conceived as a system for generating 3-D sound primarily in cinemas equipped with one of the current multichannel digital audio systems. The paper covers a simplified and relatively easily applicable variant of the system, which assumes a certain rearrangement of loudspeakers needed for surround sound reproduction in such modern theaters. The physical basis here is provided by certain psycho-acoustic laws, as well as an interesting experiment, related to the human ear's reaction to translating the so-called virtual sound source in the vertical plane. The paper also provides in general terms some of the possibilities of using this concept in the consumer technology, such as home video systems, PC multimedia, Interactive Video Games and so forth.
Increasing the capacity of parvovirus‐retentive membranes: performance of the Viresolve™ Prefilter (2005)

Removal of small parvoviruses from highly purified proteins can be performed using normal-flow filters. The entrapment of protein aggregates, denatured proteins and other impurities can cause plugging and a decrease in filter capacity. In the present study a variety of prefilters were investigated for their ability to remove the species that foul Viresolvetrade mark NFP (normal-flow parvovirus) filters. The Viresolvetrade mark Prefilter, which utilizes entrapped diatomaceous earth to hydrophobically bind fouling species, provided a dramatic increase in virus filter capacity for solutions containing human IgG or a variety of monoclonal antibodies. We found that the component of the human IgG stream that bound to the Prefilter, when analysed using SDS/PAGE, isoelectric-focusing, size-exclusion chromatography, CD and ANS (1-anilinonaphthalene-8-sulphonate) titration, consisted of monomeric IgG variants containing more exposed hydrophobic surfaces. The bound component may represent oxidized or otherwise degraded IgG species or a subset of IgG molecules with more hydrophobic antigen-binding surfaces. The results indicate that NFP membranes do not foul solely as a result of entrapment of protein aggregates in the pore structure. The Viresolvetrade mark Prefilter has a high permeability, did not diminish protein yield and provided consistent performance between different media lots, device lots and device scales.
Genome Sequence of Yersinia pestis KIM (2002)

We present the complete genome sequence of Yersinia pestis KIM, the etiologic agent of bubonic and pneumonic plague. The strain KIM, biovar Mediaevalis, is associated with the second pandemic, including the Black Death. The 4.6-Mb genome encodes 4,198 open reading frames (ORFs). The origin, terminus, and most genes encoding DNA replication proteins are similar to those of Escherichia coli K-12. The KIM genome sequence was compared with that of Y. pestis CO92, biovar Orientalis, revealing homologous sequences but a remarkable amount of genome rearrangement for strains so closely related. The differences appear to result from multiple inversions of genome segments at insertion sequences, in a manner consistent with present knowledge of replication and recombination. There are few differences attributable to horizontal transfer. The KIM and E. coli K-12 genome proteins were also compared, exposing surprising amounts of locally colinear "backbone," or synteny, that is not discernible at the nucleotide level. Nearly 54% of KIM ORFs are significantly similar to K-12 proteins, with conserved housekeeping functions. However, a number of E. coli pathways and transport systems and at least one global regulator were not found, reflecting differences in lifestyle between them. In KIM-specific islands, new genes encode candidate pathogenicity proteins, including iron transport systems, putative adhesins, toxins, and fimbriae.
Endothelial Dysfunction: From Molecular Mechanisms to Measurement, Clinical Implications, and Therapeutic Opportunities (2008)

Endothelial dysfunction has been implicated as a key factor in the development of a wide range of cardiovascular diseases, but its definition and mechanisms vary greatly between different disease processes. This review combines evidence from cell-culture experiments, in vitro and in vivo animal models, and clinical studies to identify the variety of mechanisms involved in endothelial dysfunction in its broadest sense. Several prominent disease states, including hypertension, heart failure, and atherosclerosis, are used to illustrate the different manifestations of endothelial dysfunction and to establish its clinical implications in the context of the range of mechanisms involved in its development. The size of the literature relating to this subject precludes a comprehensive survey; this review aims to cover the key elements of endothelial dysfunction in cardiovascular disease and to highlight the importance of the process across many different conditions.
Estrogen Receptor Genotypes and Haplotypes Associated with Breast Cancer Risk (2004)

Nearly one in eight US women will develop breast cancer in their lifetime. Most breast cancer is not associated with a hereditary syndrome, occurs in postmenopausal women, and is estrogen and progesterone receptor-positive. Estrogen exposure is an epidemiologic risk factor for breast cancer and estrogen is a potent mammary mitogen. We studied single nucleotide polymorphisms (SNPs) in estrogen receptors in 615 healthy subjects and 1011 individuals with histologically confirmed breast cancer, all from New York City. We analyzed 13 SNPs in the progesterone receptor gene (PGR), 17 SNPs in estrogen receptor 1 gene (ESR1), and 8 SNPs in the estrogen receptor 2 gene (ESR2). We observed three common haplotypes in ESR1 that were associated with a decreased risk for breast cancer [odds ratio (OR), approximately O.4; 95% confidence interval (CI), 0.2-0.8; P < 0.01]. Another haplotype was associated with an increased risk of breast cancer (OR, 2.1; 95% CI, 1.2-3.8; P < 0.05). A unique risk haplotype was present in approximately 7% of older Ashkenazi Jewish study subjects (OR, 1.7; 95% CI, 1.2-2.4; P < 0.003). We narrowed the ESR1 risk haplotypes to the promoter region and first exon. We define several other haplotypes in Ashkenazi Jews in both ESR1 and ESR2 that may elevate susceptibility to breast cancer. In contrast, we found no association between any PGR variant or haplotype and breast cancer. Genetic epidemiology study replication and functional assays of the haplotypes should permit a better understanding of the role of steroid receptor genetic variants and breast cancer risk.
The Major Astrocytic Phosphoprotein PEA-15 Is Encoded by Two mRNAs Conserved on Their Full Length in Mouse and Human (1996)

Specific phosphoproteins are targets of numerous extracellular signals received by astrocytes. One such target, which we previously described, is PEA-15, a protein kinase C substrate associated with microtubules. Two cDNAs differing in the length of their 3'-untranslated region (3'UTR) were cloned from a mouse astrocytic library. Accordingly, Northern blots revealed two transcripts (1.7 and 2.5 kilobase pairs) abundant brain regions but also found in peripheral tissues. PEA-15-deduced protein sequence (130 amino acids) shared no similarity with known proteins but is 96% identical to its human counterpart. In addition, several regions of the 3'UTR share more than 90% identity between mouse and human. Different potential regulatory sequences are found in the 3'UTR, which also completely includes the proto-oncogene MAT1. The high level of conservation of both the coding and the untranslated regions and the differential tissular distribution of the two transcripts of this major brain phosphoprotein suggest that not only the protein but also the 3'UTR of PEA-15 mRNA play a role in astrocytic functions.
Citrate Cycle and Related Metabolism ofListeria monocytogenes (1971)

The growth response of Listeria monocytogenes strains A4413 and 9037-7 to carbohydrates was determined in a defined medium. Neither pyruvate, acetate, citrate, isocitrate, alpha-ketoglutarate, succinate, fumarate, nor malate supported growth. Furthermore, inclusion of any of these carbohydrates in the growth medium with glucose did not increase the growth of Listeria over that observed on glucose alone. Resting cell suspensions of strain A4413 oxidized pyruvate but not acetate, citrate, isocitrate, alpha-ketoglutarate, succinate, fumarate, or malate. Cell-free extracts of strain A4413 contained active citrate synthase, aconitate hydratase, isocitrate dehydrogenase, malate dehydrogenase, fumarate hydratase, fumarate reductase, pyruvate dehydrogenase system, and oxidases for reduced nicotinamide adenine dinucleotide and reduced nicotinamide adenine dinucleotide phosphate. The alpha-ketoglutarate oxidation system, succinate dehydrogenase, isocitrate lyase, and malate synthase were not detected. Cytochromes were not detected. The data suggest that strain A4413, under these conditions, utilizes a split noncyclic citrate pathway which has an oxidative portion (citrate synthase, aconitate hydratase, and isocitrate dehydrogenase) and a reductive portion (malate dehydrogenase, fumarate hydratase, and fumarate reductase). This pathway is probably important in biosynthesis but not for a net gain in energy.
Inhibition of Leukotriene (SRS‐A)‐Mediated Acute Lung Anaphylaxis by Azelastine in Guinea Pigs (1986)

Azelastine hydrochloride, chemically known as 1(2H)-phthalazinone, 4-[(4-chlorophenyl)methyl]-2-(hexahydro-1-methyl-1H-azepine-4-yl)-, monohydrochloride, is a novel, orally effective, long-acting, antiallergic/antiasthmatic agent. The ability of azelastine and selected antiallergic drugs to inhibit SRS-A (leukotriene)-mediated acute lung anaphylaxis in guinea pigs (Konzett-Rossler method) was investigated. Azelastine and ketotifen were administered p.o. 2 and 24 h before antigen challenge; disodium cromoglycate (DSCG) was administered i.v. immediately before antigen challenge. The oral dose of azelastine required to inhibit leukotriene-mediated allergic bronchospasm by 50% (ID50: mg/kg) was 0.063 at 2 h and 0.120 at 24 h. Ketotifen at a dose of 0.05 to 10 mg/kg at 2 and 24 h, p.o., as well as DSCG at a dosage of 0.3 to 10 mg/kg at 0 min, i.v., produced weak, inconsistent and nondose-related antianaphylactic effects. Azelastine is an orally effective and long-acting inhibitor of in vivo synthesis and/or release of leukotrienes.