gebhart/patrepeval huggingface dataset:
Expression of a membrane-bound form of Trypanosoma cruzi trans-sialidase in baculovirus-infected insect cells: a potential tool for sialylation of glycoproteins produced in the baculovirus-insect cells system (2001)

A chimeric protein containing the catalytic domain of Trypanosoma cruzi trans-sialidase, the transmembrane domain of the major envelope glycoprotein of the baculovirus (gp67), and the signal peptide of ecdysteroid glucosyltransferase of the baculovirus was expressed under the control of the very late promoter p10 in baculovirus-infected lepidopteran cells. The recombinant protein was found to be enzymatically active. Three days after infection, equal amounts of activity were found associated to the plasma membrane and in the infection medium, both forms having the same apparent molecular weight and being N-glycosylated. When exogenous galactosylated acceptors (lactose or asialo-alpha1-acid glycoprotein) were added in the culture medium of cells infected with the recombinant baculovirus in the presence of a sialylated donor, a sialylation could be observed. Therefore, we propose the use of trans-sialidase as a potential tool for sialylation of glycoconjugates in the baculovirus-insect cells system.
Identification of cytochrome P-450 isoforms responsible for cis-tramadol metabolism in human liver microsomes. (2001)

The metabolism of cis-tramadol has been studied in human liver microsomes and in cDNA-expressed human cytochrome P-450 (CYP) isoforms. Human liver microsomes catalyzed the NADPH-dependent metabolism of tramadol to the two primary tramadol metabolites, namely, O-desmethyl-tramadol (metabolite M1) and N-desmethyl-tramadol (metabolite M2). In addition, tramadol was also metabolized to two minor secondary metabolites (each comprising < or =3.0% of total tramadol metabolism), namely, N,N-didesmethyl-tramadol (metabolite M3) and N,O-didesmethyl-tramadol (metabolite M5). Kinetic analysis revealed that multiple CYP enzymes were involved in the metabolism of tramadol to both M1 and M2. For the high-affinity enzymes involved in M1 and M2 formation, K(m) values were 116 and 1021 microM, respectively. Subsequent reaction phenotyping studies were performed with a tramadol substrate concentration of 250 microM. In studies with characterized human liver microsomal preparations, good correlations were observed between tramadol metabolism to M1 and M2 and enzymatic markers of CYP2D6 and CYP2B6, respectively. Tramadol was metabolized to M1 by cDNA-expressed CYP2D6 and to M2 by CYP2B6 and CYP3A4. Tramadol metabolism in human liver microsomes to M1 and M2 was markedly inhibited by the CYP2D6 inhibitor quinidine and the CYP3A4 inhibitor troleandomycin, respectively. In summary, this study demonstrates that cis-tramadol can be metabolized to tramadol metabolites M1, M2, M3, and M5 in human liver microsomal preparations. By kinetic analysis and the results of the reaction phenotyping studies, tramadol metabolism in human liver is catalyzed by multiple CYP isoforms. Hepatic CYP2D6 appears to be primarily responsible for M1 formation, whereas M2 formation is catalyzed by CYP2B6 and CYP3A4.
Ligand-mediated protein degradation reveals functional conservation among sequence variants of the CUL4-type E3 ligase substrate receptor cereblon (2018)

Upon binding to thalidomide and other immunomodulatory drugs, the E3 ligase substrate receptor cereblon (CRBN) promotes proteosomal destruction by engaging the DDB1-CUL4A-Roc1-RBX1 E3 ubiquitin ligase in human cells but not in mouse cells, suggesting that sequence variations in CRBN may cause its inactivation. Therapeutically, CRBN engagers have the potential for broad applications in cancer and immune therapy by specifically reducing protein expression through targeted ubiquitin-mediated degradation. To examine the effects of defined sequence changes on CRBN's activity, we performed a comprehensive study using complementary theoretical, biophysical, and biological assays aimed at understanding CRBN's nonprimate sequence variations. With a series of recombinant thalidomide-binding domain (TBD) proteins, we show that CRBN sequence variants retain their drug-binding properties to both classical immunomodulatory drugs and dBET1, a chemical compound and targeting ligand designed to degrade bromodomain-containing 4 (BRD4) via a CRBN-dependent mechanism. We further show that dBET1 stimulates CRBN's E3 ubiquitin-conjugating function and degrades BRD4 in both mouse and human cells. This insight paves the way for studies of CRBN-dependent proteasome-targeting molecules in nonprimate models and provides a new understanding of CRBN's substrate-recruiting function.
Structural analysis of the human nov proto-oncogene and expression in Wilms tumor. (1994)

We have cloned and sequenced the nov gene (novH) which is the homolog of the chicken nov proto-oncogene overexpressed in avian nephroblastomas. The novH gene is highly conserved and encodes a putative IGF-binding protein similar to that of chicken. We report that relative to autologous normal kidney expression of novH is elevated in Wilms tumors containing predominantly stromal elements and is inversely correlated in these tumors to the expression of WT1. Our results suggest that the regulation of IGFII expression by WT1 and increase of novH in Wilms tumors might be interrelated and represent a key element in tumor development in human.
Sortilin Is the Major 110-kDa Protein in GLUT4 Vesicles from Adipocytes (1998)

Vesicles containing the glucose transporter GLUT4 from rat adipocytes contain a major protein of 110 kDa. We have isolated this protein, obtained the sequences of peptides, and cloned a large portion of its cDNA. This revealed that the protein is sortilin, a novel membrane protein that was cloned in another context from a human source while this work was in progress. Subcellular fractionation of rat and 3T3-L1 adipocytes, together with GLUT4 vesicle isolation, showed that sortilin was primarily located in the low density microsomes in vesicles containing GLUT4. Insulin caused a 1.7-fold increase in the amount of sortilin at the plasma membranes of 3T3-L1 adipocytes, as assessed by cell surface biotinylation. The expression of sortilin in 3T3-L1 cells occurred only upon differentiation. Previous characterization of sortilin has led to the suggestion that it functions to sort lumenal proteins from the trans Golgi. The significance of its insulin-stimulated increase at the cell surface and of its expression upon differentiation will require definitive delineation of its function.
Non-Hodgkin's Lymphoma Presenting as Anasarca: Probably Mediated by Tumor Necrosis Factor Alpha (TNF-α) (2000)

Two patients presented with anasarca, fevers and sweats. Subsequent evaluation revealed aggressive lymphoproliferative disease. Both patients were treated with CHOP chemotherapy. One patient responded with spontaneous, vigorous diuresis and complete resolution of the edema. She relapsed two months later with recurrent edema that responded a second time to salvage chemotherapy. The second patient died of gram positive sepsis a week after diagnosis. As anasarca is an unusual presenting symptom of non-Hodgkin's lymphoma, we postulated that the malignant cells were secreting a cytokine that resulted in "vascular leakage" of fluid and development of diffuse edema. Several serum cytokine levels were tested. Both patients had elevated TNF-alpha levels, which could have been the cause of the edema; or there might be yet another unidentified mediator that was responsible for the anasarca. We report these two cases to bring to attention the unusual nature of this presentation.
Lipoarabinomannan of Mycobacterium tuberculosisPromotes Protein Tyrosine Dephosphorylation and Inhibition of Mitogen-activated Protein Kinase in Human Mononuclear Phagocytes (1998)

Lipoarabinomannan (LAM) is a putative virulence factor of Mycobacterium tuberculosis that inhibits monocyte functions, and this may involve antagonism of cell signaling pathways. The effects of LAM on protein tyrosine phosphorylation in cells of the human monocytic cell line THP-1 were examined. LAM promoted tyrosine dephosphorylation of multiple cell proteins and attenuated phorbol 12-myristate 13-acetate-induced activation of mitogen-activated protein kinase. To examine whether these effects of LAM could be related to activation of a phosphatase, fractions from LAM-treated cells were analyzed for dephosphorylation of para-nitrophenol phosphate. The data show that LAM induced increased phosphatase activity associated with the membrane fraction. The Src homology 2 containing tyrosine phosphatase 1 (SHP-1) is important for signal termination and was examined as a potential target of LAM. Exposure of cells to LAM brought about (i) an increase in tyrosine phosphorylation of SHP-1, and (ii) translocation of the phosphatase to the membrane. Phosphatase assay of SHP-1 immunoprecipitated from LAM-treated cells, using phosphorylated mitogen-activated protein kinase as substrate, indicated that LAM promoted increased activity of SHP-1 in vivo. LAM also activated SHP-1 directly in vitro. Exposure of cells to LAM also attenuated the expression of tumor necrosis factor-alpha, interleukin-12, and major histocompatibility class II molecules. These results suggest that one mechanism by which LAM deactivates monocytes involves activation of SHP-1.
Receptor‐mediated transcytosis of transferrin across the blood‐brain barrier (1987)

The perfusion of rat brain with 125I-transferrin resulted in a receptor-mediated uptake of transferrin into the endothelium of the blood-brain barrier followed by its detection in the brain. During a pulse-chase experiment, 125I-transferrin accumulated in the endothelial cells during the pulse, with a decrease of this intraendothelial radioactivity during the chase associated with a concomitant increase in the nonvascular elements of the brain. The receptor-mediated movement of transferrin across the blood-brain barrier suggests that the brain may derive its iron through the transcytosis of iron-loaded transferrin across the brain microvasculature. We discuss the likelihood that aluminum and other potentially toxic heavy metals, which also bind tightly to transferrin, may enter the brain by this pathway. We also discuss the possibility that other large molecules including neuroactive peptides and neurotrophic viruses may enter the brain through a similar receptor-mediated, vesicular transcytotic route.
Clomiphene Citrate and Testosterone Gel Replacement Therapy for Male Hypogonadism: Efficacy and Treatment Cost (2009)

CC represents a treatment option for men with hypogonadism, demonstrating biochemical and clinical efficacy with few side effects and lower cost as compared with TGRT.
Nuclear cataract and myopia during hyperbaric oxygen therapy. (1984)

The effect on the human lens of prolonged hyperbaric oxygen therapy is reported. Eye examinations were given to 25 patients before, during, and after a series of 150 or more exposures to hyperbaric oxygen. All patients changed refraction in the direction of myopia during treatment. Fifteen of the patients had clear lens nuclei before treatment. Seven of these developed a nuclear cataract with reduced visual acuity during treatment. Reversible lens myopia has previously been noticed as a side effect of exposure to hyperbaric oxygen, but the cataractogenic effect in man has not been reported by other workers. This report strongly supports the theory of an oxidative damage to the lens proteins as a cause of nuclear cataract.
The Interaction of Boronic Acid-Substituted Viologens with Pyranine:  The Effects of Quencher Charge on Fluorescence Quenching and Glucose Response (2005)

The fluorescence sensing of several monosaccharides using boronic acid-substituted viologen quenchers in combination with the fluorescent dye pyranine (HPTS) is reported. In this two-component sensing system, fluorescence quenching by the viologen is modulated by monosaccharides to provide a fluorescence signal. A series of viologen quenchers with different charges were prepared and tested for their ability both to quench the fluorescence of HPTS and to sense changes in glucose concentration in aqueous solution at pH 7.4. Both quenching efficiency and sugar sensing were found to be strongly dependent upon viologen charge. The molar ratio between HPTS and each of the viologen quenchers was varied in order to obtain an optimal ratio that provided a fairly linear fluorescence signal across a physiological glucose concentration range. Both the quenching and sugar sensing results are explained by electrostatic interaction between dye and quencher.
Bay Area ATIS Testbed Plan (1992)

Several factors have motivated the development of Intelligent Vehicle Highway Systems (IVHS); among them are growing traffic congestion, concern for environmental degradation, the need to improve safety, and the desire to best utilize existing transportation infrastructure. Within the framework of M-IS, Advanced Traveler Information Systems (ATIS) will provide historical, real-time and predictive information to support travel decisions. ATIS offers significant benefits interms of improving the travel experience of individuals and enhancing system performance. In the long-term, ATIS may reduce congestion and pollution, improve safety and increase mobility. However, the true potential of these systems has not been evaluated. To do this, an ATIS testbed in the Bay Area is proposed.
The refdbms distributed bibliographic database system (1994)

Refdbms is a database system for sharing bibliographic references among many users at sites on a wide-area network such as the Internet. This paper describes our experiences in building and using refdbms for the last two years. It summarizes the collection of facilities that refdbms provides, and gives detailed information on how well refdbms functions as a collaborative, wide-area, distributed information system.
Analysis of the Contraceptive Potential of Antibodies against Native and Deglycosylated Porcine ZP3 in Vivo and in Vitro1 (1992)

We have undertaken a comparative analysis of the contraceptive activity of antibodies directed against the porcine sperm receptor zona pellucida antigen (ZP3) and its Mr = 32,000 polypeptide core (DGZP-32). The strategies employed for this analysis included the induction of active immunity in a primate, the common marmoset, and an in vitro fertilization protocol involving the use of viable human ova. In both experimental situations, antibodies against ZP3 were shown to exhibit contraceptive activity, leading respectively to the induction of long-term infertility in the primate model and to the complete inhibition of human fertilization in vitro. The in vivo studies also revealed that the induction of high titer antibodies against ZP3 was inevitably associated with the appearance of an ovarian pathology characterized by the progressive depletion of the primordial follicle pool within one to two years. This side effect could not be alleviated by the use of DGZP-32 as antigen since the induction of immunity against this polypeptide was also associated with the eventual appearance of an ovarian pathology identical to that observed with ZP3. Furthermore, the DGZP-32 peptide was less effective than ZP3 in inducing the formation of antibodies capable of inhibiting the fertilization of human ova in vitro. We conclude that significant problems remain with the use of deglycosylated zona peptides for the development of contraceptive vaccines and that their potential will not be realized until the epitopes responsible for the induction of infertility and the primordial follicle depletion have been identified and segregated.
The Cubetree Storage Organization (1998)

The Relational On-Line Analytical Processing (ROLAP) is emerging as the dominant approach in data warehousing. In order to enhance query performance, the ROLAP approach relies on selecting and materializing in summary tables appropriate subsets of aggregate views which are then engaged in speeding up OLAP queries. However, a straight forward relational storage implementation of materialized ROLAP views is immensely wasteful on storage and incredibly inadequate on query performance and incremental update speed.
Effect of Mechanical Stress on p-n Junction Device Characteristics (1964)

A theoretical model is developed for the effect of mechanical stress on the electrical characteristics of Ge and Si p-n junction devices. This model is based upon the stress-induced variations in energy band structure and their effect on minority carrier densities. The changes in minority carrier densities are shown to depend upon the type of stress applied, with anisotropic stresses causing larger changes than hydrostatic stresses. From the calculated dependence of minority carrier densities upon stress, the equations are developed for the current—voltage characteristics of diodes and transistors under stress. Following the general analysis several examples are given in which stress is applied to a small section of a junction in a diode or transistor. The results show that at stress levels greater than 1010 dyn/cm2, the device currents can change by several orders of magnitude when stress levels are changed by a factor of 2. The theory is compared with published experimental data and found to be in good agreement.
Electron-beam-induced deformations of SiO2 nanostructures (2005)

The imaging beam of a transmission electron microscope can be used to fine tune critical dimensions in silicon oxide nanostructures. This technique is particularly useful for the fabrication of nanopores with single-nanometer precision, down to 2 nm. We report a detailed study on the effect of electron-beam irradiation on apertures with various geometries. We show that, on the same wafer, pores that are smaller than a certain critical size shrink and that larger ones expand. Our results are in agreement with the hypothesis that surface-tension effects drive the modifications. Additionally, we have determined the chemical composition in the pore region before and after modifications and found no significant changes. This result proves that contamination growth is not the underlying mechanism of pore closure.
Mode of Glucocorticoid Actions in Airway Disease (2006)

Synthetic glucocorticoids are the most potent anti-inflammatory agents used to treat chronic inflammatory disease, such as asthma. However, a small number (<5%) of asthmatic patients and almost all patients with chronic obstructive pulmonary disease (COPD) do not respond well, or at all, to glucocorticoid therapy. If the molecular mechanism of glucocorticoid insensitivity is uncovered, it may in turn provide insight into the key mechanism of glucocorticoid action and allow a rational way to implement treatment regimens that restore glucocorticoid sensitivity. Glucocorticoids exert their effects by binding to a cytoplasmic glucocorticoid receptor (GR), which is subjected to post-translational modifications. Receptor phosphorylation, acetylation, nitrosylation, ubiquitinylation, and other modifications influence hormone binding, nuclear translocation, and protein half-life. Analysis of GR interactions to other molecules, such as coactivators or corepressors, may explain the genetic specificity of GR action. Priming with inflammatory cytokine or oxidative/nitrative stress is a mechanism for the glucocorticoid resistance observed in chronic inflammatory airway disease via reduction of corepressors or GR modification. Therapies targeting these aspects of the GR activation pathway may reverse glucocorticoid resistance in patients with glucocorticoid-insensitive airway disease and some patients with other inflammatory diseases, such as rheumatoid arthritis and inflammatory bowel disease.
Role of salvage and phosphorylation in the immunostimulatory activity of C8-substituted guanine ribonucleosides. (1988)

Lymphokine-like activity and selective stimulation of B cell growth is exerted by a group of synthetic ribonucleosides derivatized at C8 and exemplified by 8-bromoguanosine (8BrGuo), 8-mercaptoguanosine, and 7-methyl 8-oxoguanosine. However, relatively little is known about their molecular mechanism of action. Like naturally occurring nucleosides, 8BrGuo is taken up into lymphocytes by a process of facilitated diffusion. Naturally occurring nucleosides are then reclaimed by a well characterized salvage pathway, involving sequential phosphorolysis and phosphoribosylation. The studies reported in this communication demonstrate that, in contrast to naturally occurring nucleosides, 8BrGuo is not a substrate for salvage by purine nucleoside phosphorylase. The base that would be produced by putative phosphorolysis, 8-bromoguanine, is biologically inactive and is not a substrate for hypoxanthine-guanine phosphoribosyl-transferase. Accordingly, inhibitors of purine nucleoside phosphorylase-mediated salvage fail to inhibit nucleoside-induced immunostimulation selectively. Examination of the metabolism of 8BrGuo provides no direct evidence that 8BrGuo is phosphorylated by B lymphocytes. Direct enzymatic phosphorylation does not seem to be essential to the mechanism of action of the nucleoside insofar as competitive inhibition of deoxycytidine kinase (an enzyme that directly phosphorylates purines as well as pyrimidines) or of deoxyguanosine kinase fails to inhibit 8BrGuo stimulation selectively. Moreover, studies with synthetic nucleosides in which 3' and/or 5' hydroxyl groups were irreversibly blocked, precluding their phosphorylation, demonstrated that immunobiologic activity can occur in the absence of 3' and/or 5' phosphorylation. Finally, experiments with radiolabeled nucleosides provide no evidence to support the hypothesis that they are incorporated into cellular nucleic acid. These data, together with previous studies, suggest that it is the unmetabolized nucleoside that is active and, as such, is most likely to act in a regulatory capacity.