gebhart/patrepeval huggingface dataset:
Differential Function of the Prolyl Hydroxylases PHD1, PHD2, and PHD3 in the Regulation of Hypoxia-inducible Factor (2004)

Hypoxia-inducible factor (HIF) is a transcriptional regulator that plays a key role in many aspects of oxygen homeostasis. The heterodimeric HIF complex is regulated by proteolysis of its alpha-subunits, following oxygen-dependent hydroxylation of specific prolyl residues. Although three HIF prolyl hydroxylases, PHD1, PHD2, and PHD3, have been identified that have the potential to catalyze this reaction, the contribution of each isoform to the physiological regulation of HIF remains uncertain. Here we show using suppression by small interference RNA that each of the three PHD isoforms contributes in a non-redundant manner to the regulation of both HIF-1alpha and HIF-2alpha subunits and that the contribution of each PHD under particular culture conditions is strongly dependent on the abundance of the enzyme. Thus in different cell types, isoform-specific patterns of PHD induction by hypoxia and estrogen alter both the relative abundance of the PHDs and their relative contribution to the regulation of HIF. In addition, the PHDs manifest specificity for different prolyl hydroxylation sites within each HIF-alpha subunit, and a degree of selectively between HIF-1alpha and HIF-2alpha isoforms, indicating that differential PHD inhibition has the potential to selectively alter the characteristics of HIF activation.
Cloning of rat lymphocyte activation gene‐3 (Lag3; CD223) cDNA and its mRNA expression in rat tissues* (2004)

Rat lymphocyte activation gene-3 (Lag3; CD223) cDNA contains an open reading frame (1575 bp) encoding 525 amino acids. Rat Lag3 mRNA transcript was detected as a single species of approximately 2 kb from phytohemagglutinin (PHA)-stimulated lymphocytes. Further analysis revealed that rat Lag3 mRNA was mainly expressed in lymphoid tissues.
Antisense therapy (1996)

The sequence specificity of the antisense technique makes it an attractive basis for novel molecular therapeutics. Inhibition of gene expression by antisense in cell culture models has provided a strong rationale for identification and validation of disease targets. Analogues modified from normal phosphodiester oligodeoxynucleotides have entered clinical trials of diseases including AIDS, cancer, and inflammation. It is becoming increasingly apparent that these drugs act by means of a complex mechanism of action, and some of their effects can be sequence independent. Nevertheless, these oligodeoxynucleotides offer considerable promise as novel molecular drugs. Harnessing the therapeutic potential of this powerful technique depends on elucidation of the complex mechanism of action so that effective and meaningful therapeutic modalities can be realized.
Chronic morphine administration induces tolerance to suppressive morphine effects in two canonical LPS-induced innate immunity responses in mice. (162.20) (2011)

Abstract The immunosuppressive effects of acute morphine administration are well described. However, little is known about chronic morphine treatment actions using different administration schedules. The aim of this work was to study the effects of various morphine administration schemes on peritoneal Tumor Necrosis Factor-α (TNF-α) release and serum corticosterone levels after i.p. injection of bacterial lipopolysaccharide (LPS) in mice. Our results show that morphine per se (0.1-10 mg/kg) had no effects on TNF-α levels. Morphine inhibited LPS-induced TNF-α release but this effect occurred only at high doses (3.1 y 10 mg/kg) and was not dose dependent. Serum corticosterone levels increased after a single LPS challenge and morphine dose-dependently prevented this effect. After repeated administration, tolerance developed to the inhibitory effects of morphine on peritoneal TNF-α release and serum corticosterone levels in response to LPS. These data suggest that morphine inhibitory effects on innate immunity depend on the opioid administration schedule and duration treatment.
Expression of diphtheria toxin fragment A and hormone-toxin fusion proteins in toxin-resistant yeast mutants. (1988)

Mutants of the eukaryote Saccharomyces cerevisiae, previously selected for resistance to diphtheria toxin, were investigated for their suitability as hosts for the expression of tox-related proteins. The structural gene for the toxin, encoding the fragment A catalytic domain, was modified for efficient intracellular expression in eukaryotes and placed downstream of the yeast GAL1 promoter element in a plasmid. Transformed mutant yeast grown in galactose, which induces that promoter, were viable and contained active fragment A. In contrast, sensitive, wild-type cells harboring this plasmid grew normally under repressing conditions but were killed when the GAL1 promoter was induced. Additional constructions were also prepared that included sequences encoding either the lymphocyte growth factor interleukin 2 or alpha-melanocyte-stimulating hormone along with the lipid-associating domains of fragment B and the leader peptide of the Kluyveromyces lactis killer toxin. Resistant mutant strains transformed with these plasmids efficiently expressed and secreted the expected chimeric toxins.
6‐Ethyl‐N,N′‐bis(3‐hydroxyphenyl)[1,3,5]triazine‐2,4‐diamine (RS‐0466) Enhances the Protective Effect of Brain‐Derived Neurotrophic Factor on Amyloid β‐Induced Cytotoxicity in Cortical Neurones (2003)

Amyloid beta peptide in the senile plaques of patients with Alzheimer's disease is considered to be responsible for the pathology of Alzheimer's disease. We have previously reported that 6-ethyl-N,N'-bis(3-hydroxyphenyl)[1,3,5]triazine-2,4-diamine, RS-0466, is capable of significantly inhibiting amyloid beta-induced cytotoxicity in HeLa cells. To determine various profiles of RS-0466, we investigated whether RS-0466 would enhance the neuroprotective effect of brain-derived neurotrophic factor on amyloid beta(1-42)-induced cytotoxicity in rat cortical neurones. Consistent with previous observations, brain-derived neurotrophic factor ameliorated amyloid beta(1-42)-induced cytotoxicity. Furthermore, co-application of RS-0466 enhanced the neuroprotective effect of brain-derived neurotrophic factor. RS-0466 also reversed amyloid beta(1-42)-induced decrease of brain-derived neurotrophic factor-triggered phosphorylated Akt. These results raise the possibility that RS-0466 or one of its derivatives has potential to enhance the neuroprotective effect of brain-derived neurotrophic factor, and could serve as a therapeutic agent for patients with Alzheimer's disease.
Investigation of Smaller-Footprint Drilling System; Ultrahigh-Rotary-Speed Diamond Drilling Has Potential for Reduced Energy Requirements (2006)

Abstract This paper describes proof of concept testing of an ultra-high rotary speed drilling system and its applicability to hard rock drilling performance. The drilling system includes the use of thin-walled diamond bits driven at extremely high rotational speeds. This program is partly funded by the DOE. Results from this study demonstrate the feasibility, verification, and characterization of the system combining high speed and sharp, low depth of cut diamond bits. This is leading edge technology. The review of industry practices has shown that in general, rotational speeds above 1000 RPM have not been utilized in the drilling of oil and gas wells. Rotational speeds from 1000 to 50,000 RPM are used to machine or remove hard materials in other applications. These materials are removed efficiently using high RPM and small thrust loads. The drilling and coring industry does not currently practice this technology. The paper presents data and resulting drilling performance of a number of specially designed thin wall diamond core heads in a variety of rock formations tested at bench scale. The results show rates of penetration in different rock types while calculating expended energy. Most promising are specific energies that decrease at higher face velocities, possibly showing that rock failure mechanisms change. The significance of a smaller footprint drilling system is the ability to drill into rock with low weights on bit and at low energy levels while maintaining high rates of penetration. For many operators, high well construction costs occur in hard rock areas. An improvement in penetration rates while minimizing expended energy is an opportunity to reduce drilling costs and drastically improve project economics. The estimated annual cost to drill hard rock in North America is in excess of $1.2 billion. Testing of full-face bits is the next step. Future applications may include slim hole drilling with downhole electrical, PDM, or turbine drives though some operators view better performance is also possible in conventional hole sizes such as 8-1/2 inch. Adaptation to the oilfield will require innovative bit designs for full hole drilling or continuous coring and the eventual development of these downhole ultra-high speed drives.
Platinum Group Metals and Compounds (1971)

Although they are paramagnetic, the platinum metals, especially platinum, palladium, and rhodium, are capable of interacting in alloys with other metals to form ferromagnetic or very nearly ferromagnetic materials. Dilute additions of elements of the iron group and its neighbors with platinum and palladium take on enhanced moments which are interpreted as arising from an interaction of the solute moment with the 4d or 5d host electrons. Ferromagnetic and anti-ferromagnetic structures may result from greater additions of the iron group to the platinum metals. Examples are FeRh, Pt3Fe, Pd3Fe, and PtCo. Compounds of the rare earths with the platinum metals also form magnetic structures with unusual properties.
Deficient Peptide Loading and MHC Class II Endosomal Sorting in a Human Genetic Immunodeficiency Disease: the Chediak-Higashi Syndrome (1998)

The Chediak-Higashi syndrome (CHS) is a human recessive autosomal disease caused by mutations in a single gene encoding a protein of unknown function, called lysosomal-trafficking regulator. All cells in CHS patients bear enlarged lysosomes. In addition, T- and natural killer cell cytotoxicity is defective in these patients, causing severe immunodeficiencies. We have analyzed major histocompatibility complex class II functions and intracellular transport in Epstein Barr Virus-transformed B cells from CHS patients. Peptide loading onto major histocompatibility complex class II molecules and antigen presentation are strongly delayed these cells. A detailed electron microscopy analysis of endocytic compartments revealed that only lysosomal multilaminar compartments are enlarged (reaching 1-2 micron), whereas late multivesicular endosomes have normal size and morphology. In contrast to giant multilaminar compartments that bear most of the usual lysosomal markers in these cells (HLA-DR, HLA-DM, Lamp-1, CD63, etc.), multivesicular late endosomes displayed reduced levels of all these molecules, suggesting a defect in transport from the trans-Golgi network and/or early endosomes into late multivesicular endosomes. Further insight into a possible mechanism of this transport defect came from immunolocalizing the lysosomal trafficking regulator protein, as antibodies directed to a peptide from its COOH terminal domain decorated punctated structures partially aligned along microtubules. These results suggest that the product of the Lyst gene is required for sorting endosomal resident proteins into late multivesicular endosomes by a mechanism involving microtubules.
A multiple access technique for centralized multiple satellite networking with on-board processing in the central node (2003)

The authors defines multiple-access method suitable for a centralized multiple satellite network, with onboard processing in the central node. This multiple-access method (CDMA/Aloha/BFN) is a combination of code-division multiple-access (CDMA), random multiple access (RMA) or Aloha, and a set of electronic beam forming networks (BFN). CDMA/Aloha/BFN multiple access maintains the advantages of CDMA and RMA techniques and avoids their disadvantages by using some processing on board the central satellite stations. The major characteristics of this method are: no need for network synchronization resistance to jamming, efficient use of the available system power and bandwidth, low equipment complexity, low mutual interference, ability to operate in systems supporting highly dynamic users, and good delay-throughput performance. The theory of operation of the CDMA/Aloha/BFN multiple-access technique is described and its performance is analyzed.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Idiotype-pulsed dendritic cell vaccination for B-cell lymphoma: clinical and immune responses in 35 patients (2002)

Tumor-specific clonal immunoglobulin expressed by B-cell lymphomas (idiotype [Id]) can serve as a target for active immunotherapy. We have previously described the vaccination of 4 patients with follicular lymphoma using dendritic cells (DCs) pulsed with tumor-derived Id protein and now report on 35 patients treated using this approach. Among 10 initial patients with measurable lymphoma, 8 mounted T-cell proliferative anti-Id responses, and 4 had clinical responses--2 complete responses (CRs) (progression-free [PF] for 44 and 57 months after vaccination), 1 partial response (PR) (PF for 12 months), and 1 molecular response (PF for 75+ months). Subsequently, 25 additional patients were vaccinated after first chemotherapy, and 15 of 23 (65%) who completed the vaccination schedule mounted T-cell or humoral anti-Id responses. Induction of high-titer immunoglobulin G anti-Id antibodies required coupling of Id to the immunogenic carrier protein keyhole limpet hemocyanin (Id-KLH). These antibodies could bind to and induce tyrosine phosphorylation in autologous tumor cells. Among 18 patients with residual tumor at the time of vaccination, 4 (22%) had tumor regression, and 16 of 23 patients (70%) remain without tumor progression at a median of 43 months after chemotherapy. Six patients with disease progression after primary DC vaccination received booster injections of Id-KLH protein, and tumor regression was observed in 3 of them (2 CRs and 1 PR). We conclude that Id-pulsed DC vaccination can induce T-cell and humoral anti-Id immune responses and durable tumor regression. Subsequent boosting with Id-KLH can lead to tumor regression despite apparent resistance to the primary DC vaccine.
High protection of animals lethally infected with influenza virus by aprotinin‐rimantadine combination (1987)

The successful therapeutic synergism of aprotinin and rimantadine, which are known to attack different viral targets, was demonstrated in influenza-virus-infected animals. Combined treatment with these drugs of mice infected with a highly lethal dose of mouse-adapted influenza virus prevented the development of fatal haemorrhagic pneumonia and protected about 75% of animals; whereas the separate administration of aprotinin and rimantadine induced 35% and 15% protection, respectively.
Controlling Mammalian Gene Expression by Allosteric Hepatitis Delta Virus Ribozymes (2013)

We engineered small molecule responsive allosteric ribozymes based on the genomic hepatitis delta virus (HDV) ribozyme by replacing the P4-L4 stem-loop with an RNA aptamer through a connector stem. When embedded in the 3' untranslated region of a reporter gene mRNA, these RNA devices enabled regulation of cis-gene expression by theophylline and guanine by up to 29.5-fold in mammalian cell culture. Furthermore, a NOR logic gate device was constructed by placing two engineered ribozymes in tandem, demonstrating the modularity of the RNA devices. The significant improvement in the regulatory dynamic range (ON/OFF ratio) of the RNA devices based on the HDV ribozyme should provide new opportunities for practical applications.
Determination of the Stability of Asphaltenes Through Physicochemical Characterization of Asphaltenes (2016)

Abstract Significant effort has been dedicated to understand the variables affecting asphaltene precipitation. Based on years of research, it is well known how variables such as temperature and pressure can affect the deposition of asphaltenes. However, much less is understood about the effect that asphaltene characteristics have on the tendency towards precipitation of different crude oils. We characterize extensively a series of n-pentane extracted asphaltenes and construct novel correlations with the stability of their corresponding crude oils. 11 different bitumen and crude oil samples are characterized first with API gravity and viscosity measurements, and thermogravimetric and differential scanning calorimetric analyses (TGA/DSC). The weight percentage of the asphaltenes in bulk samples are determined through n-pentane precipitation. The molecular structure of the asphaltenes is investigated with Fourier Transform InfraRed (FTIR) spectroscopy. Asphaltene stability is measured by ΔPS and by determining the Asphaltene Solubility Profile. The impact of hydrogen deficiency, heteroatom content and solubility distributions on other properties such as viscosity and aggregation behavior is also explored. It has been observed that there is weak relationship between the asphaltene content and API gravity or viscosity of the bulk samples. The weight percent of the light, intermediate, heavy, solid, and ash fractions of the asphaltenes, defined with TGA/DSC experiments, indicate that the carbon rich solid component of the bulk samples that can decompose over 550 °C, correlate with the weight percent of the asphaltenes in bulk oil. The ash content of the bulk oil, which is mainly composed of heavy metals like sulfur, nickel, and vanadium, is correlated to the amount of asphaltenes precipitated out of the oil. Moreover, FTIR and solubility profile analyses reveals that the polarity of the asphaltene molecules is affected not only by its molecular composition and structure but also by its interactions with other crude oil components. This study discusses the impact of the physical and chemical properties of crude oils and their asphaltenes on asphaltene precipitation. Several asphaltene deposition mechanisms are developed and validated for 11 different crude oil and bitumen samples with different asphaltene contents, thereby providing important and fundamental insight into asphaltene related problems.
Ovarian steroid hormones regulate granulocyte-macrophage colony- stimulating factor synthesis by uterine epithelial cells in the mouse (1996)

Uterine epithelial cells have been shown by in vitro studies to be a potent source of the inflammatory cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF), and the luminal and glandular epithelium has been confirmed as the predominant site of GM-CSF expression in the intact endometrium by in situ hybridization. To examine the role of ovarian steroid hormones in GM-CSF synthesis, GM-CSF bioactivity has been measured in the supernatants of short-term primary cultures of endometrial cells prepared from mice in which steroid levels were perturbed by ovariectomy and steroid replacement or by steroid antagonists. GM-CSF production was found to fluctuate in cells harvested at different times during the estrous cycle, peaking at estrus. Endometrial cells derived from ovariectomized mice produced 25-fold less GM-CSF than did cells from estrous mice, and production was increased if ovariectomized mice were pretreated with estrogen, but not progesterone, 3 h or more before harvest. This estrogen-induced increase was inhibited by coadministration of progesterone or by induction of a decidual response and was blocked by the estrogen antagonist ZK 119,010. By contrast, pretreatment of mice with the anti-progestin RU486 significantly elevated GM-CSF output in cells from ovariectomized mice given estrogen and progesterone in combination and antagonized the inhibition of GM-CSF release seen in cells harvested from mice treated with hCG. These studies demonstrate that GM-CSF synthesis and/or release by uterine epithelial cells is stimulated by estrogen, with progesterone having a moderate inhibitory effect. Analysis of GM-CSF mRNA expression in uterine epithelial cell cultures and in intact uteri from steroid hormone-treated ovariectomized mice by quantitative reverse transcription-polymerase chain reaction indicated that the effects of estrogen and progesterone on GM-CSF release are mediated at least in part at the transcriptional level. These findings implicate GM-CSF as a local mediator of steroid-driven remodeling events in the cycling and preimplantation endometrium, possibly acting through the recruitment and behavioral regulation of granulocytes and macrophages.
Wilms' Tumor Gene Expression by Normal and Malignant Human B Lymphocytes (2000)

Very little is known about Wilms' tumor gene (WT1) expression in B cells and its importance for growth regulation and differentiation. We have investigated WT1 expression in fresh B lymphocytes and in a panel of B-cell lines of normal and malignant origin, including both Epstein-Barr virus (EBV) genome negative and EBV carrying cell lines. WT1 is constitutively activated in all lymphoblastoid cell lines (LCL) derived from EBV immortalization of lymphocytes from normal donors in vitro. These cell lines are distinguished for the presence of activated B-cell markers and an unrestricted expression of viral latent genes. In contrast, WT1 expression is abrogated in normal B lymphocytes and in all Burkitt tumor derived cell lines, irrespective of the EBV genome carrying status and their phenotype pattern. A single step RT-PCR for simultaneous detection of the four spliced transcript isoforms has been applied to confirm their expression. Analysis of variant relative proportions suggested the maintenance of a balanced expression of the isoforms in LCL, as reported in non tumorous tissues. These data, together with the evidence that the replication in vitro of lymphoblastoid cells is not affected by WT1 activation following viral immortalization, support the hypothesis that gene inactivation, in addition to disrupted alternate splicing, may play a role in growth control derangements.
Enantioselective Amino Acid Synthesis by Chiral Phase-Transfer Catalysis (2003)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTEnantioselective Amino Acid Synthesis by Chiral Phase-Transfer CatalysisKeiji Maruoka and Takashi OoiView Author Information Department of Chemistry, Graduate School of Science, Kyoto University, Sakyo, Kyoto 606-8502, Japan Cite this: Chem. Rev. 2003, 103, 8, 3013–3028Publication Date (Web):June 13, 2003Publication History Received16 January 2003Published online13 June 2003Published inissue 1 August 2003https://pubs.acs.org/doi/10.1021/cr020020ehttps://doi.org/10.1021/cr020020eresearch-articleACS PublicationsCopyright © 2003 American Chemical SocietyRequest reuse permissionsArticle Views12540Altmetric-Citations780LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose SUBJECTS:Alcohols,Catalysts,Organic compounds,Peptides and proteins,Post-translational modification Get e-Alerts