gebhart/patrepeval huggingface dataset:
Multiple types of skeletal muscle atrophy involve a common program of changes in gene expression (2004)

Skeletal muscle atrophy is a debilitating response to starvation and many systemic diseases including diabetes, cancer, and renal failure. We had proposed that a common set of transcriptional adaptations underlie the loss of muscle mass in these different states. To test this hypothesis, we used cDNA microarrays to compare the changes in content of specific mRNAs in muscles atrophying from different causes. We compared muscles from fasted mice, from rats with cancer cachexia, streptozotocin-induced diabetes mellitus, uremia induced by subtotal nephrectomy, and from pair-fed control rats. Although the content of >90% of mRNAs did not change, including those for the myofibrillar apparatus, we found a common set of genes (termed atrogins) that were induced or suppressed in muscles in these four catabolic states. Among the strongly induced genes were many involved in protein degradation, including polyubiquitins, Ub fusion proteins, the Ub ligases atrogin-1/MAFbx and MuRF-1, multiple but not all subunits of the 20S proteasome and its 19S regulator, and cathepsin L. Many genes required for ATP production and late steps in glycolysis were down-regulated, as were many transcripts for extracellular matrix proteins. Some genes not previously implicated in muscle atrophy were dramatically up-regulated (lipin, metallothionein, AMP deaminase, RNA helicase-related protein, TG interacting factor) and several growth-related mRNAs were down-regulated (P311, JUN, IGF-1-BP5). Thus, different types of muscle atrophy share a common transcriptional program that is activated in many systemic diseases.
New Mechanism for Release of Endosomal Contents: Osmotic Lysis via Nigericin-Mediated K+/H+ Exchange (2018)

Although peptides, antibodies/antibody fragments, siRNAs, antisense DNAs, enzymes, and aptamers are all under development as possible therapeutic agents, the breadth of their applications has been severely compromised by their inability to reach intracellular targets. Thus, while macromolecules can often enter cells by receptor-mediated endocytosis, their missions frequently fail due to an inability to escape their entrapping endosomes. In this paper, we describe a general method for promoting release of any biologic material from any entrapping endosome. The strategy relies on the fact that all nascent endosomes contain extracellular (Na<sup>+</sup>-enriched) medium, but are surrounded by intracellular (K<sup>+</sup>-enriched) fluid in the cytoplasm. Osmotic swelling and rupture of endosomes will therefore be facilitated if the flow of K<sup>+</sup> down its concentration gradient from the cytosol into the endosome can be facilitated without allowing downhill flow of Na<sup>+</sup> from the endosome into the cytosol. While any K<sup>+</sup> selective ionophore can promote the K<sup>+</sup> specific influx, the ideal K<sup>+</sup> ionophore will also exchange influxed K<sup>+</sup> for an osmotically inactive proton (H<sup>+</sup>) in order to prevent buildup of an electrical potential that would rapidly halt K<sup>+</sup> influx. The only ionophore that catalyzes this exchange of K<sup>+</sup> for H<sup>+</sup> efficiently is nigericin. We demonstrate here that ligand-targeted delivery of nigericin into endosomes that contain an otherwise impermeable fluorescent dye can augment release of the dye into the cell cytosol via swelling/bursting of the entrapping endosomes. We further show that nigericin-facilitated escape of a folate-targeted luciferase siRNA conjugate from its entrapping endosomes promotes rapid suppression of the intended luciferase reporter gene. Taken together, we propose that ionophore-catalyzed entry of K<sup>+</sup> into endosomal compartments can promote the release of otherwise impermeable contents from their encapsulating endosomes.
The protective effect of IFN-gamma in experimental autoimmune diseases: a central role of mycobacterial adjuvant-induced myelopoiesis. (2000)

The study of animal models for organ-specific autoimmune disease contributes to our understanding of human diseases such as multiple sclerosis and rheumatoid arthritis. Although experimental autoimmune diseases develop spontaneously in certain strains of mice, others need to be induced by administration of organ-specific autoantigen, often together with complete Freund's adjuvant (CFA), containing heat-killed mycobacteria. In the two types of models, the role of endogenous interferon-gamma (IFN-gamma) has extensively been investigated by using neutralizing anti-IFN-gamma antibodies and by employing mice genetically deficient in IFN-gamma or its receptor. In these studies disease-promoting as well as disease-protective roles of endogenous IFN-gamma have been described. Remarkably, in most models that rely on the use of CFA, there is abundant evidence for a protective role. Here, we review evidence that this role derives from an inhibitory effect of IFN-gamma on myelopoiesis elicited by the killed mycobacteria. These findings explain the bimodal role of IFN-gamma in different models of autoimmune disease and raise questions regarding the clinical relevance of these models.
Proteome analysis using selective incorporation of isotopically labeled amino acids (2000)

A method is described for identifying intact proteins from genomic databases using a combination of accurate molecular mass measurements and partial amino acid content. An initial demonstration was conducted for proteins isolated from Escherichia coli (E. coli) using a multiple auxotrophic strain of K12. Proteins extracted from the organism grown in natural isotopic abundance minimal medium and also minimal medium containing isotopically labeled leucine (Leu-D10), were mixed and analyzed by capillary isoelectric focusing (CIEF) coupled with Fourier transform ion cyclotron resonance mass spectrometry (FTICR). The incorporation of the isotopically labeled Leu residue has no effect on the CIEF separation of the protein, therefore both versions of the protein are observed within the same FTICR spectrum. The difference in the molecular mass of the natural isotopic abundance and Leu-D10 isotopically labeled proteins is used to determine the number of Leu residues present in that particular protein. Knowledge of the molecular mass and number of Leu residues present can be used to unambiguously identify the intact protein. Preliminary results show the efficacy of this method for unambiguously identifying proteins isolated from E. coli.
Association of Microbial Community Composition and Activity with Lead, Chromium, and Hydrocarbon Contamination (2002)

Microbial community composition and activity were characterized in soil contaminated with lead (Pb), chromium (Cr), and hydrocarbons. Contaminant levels were very heterogeneous and ranged from 50 to 16,700 mg of total petroleum hydrocarbons (TPH) kg of soil(-1), 3 to 3,300 mg of total Cr kg of soil(-1), and 1 to 17,100 mg of Pb kg of soil(-1). Microbial community compositions were estimated from the patterns of phospholipid fatty acids (PLFA); these were considerably different among the 14 soil samples. Statistical analyses suggested that the variation in PLFA was more correlated with soil hydrocarbons than with the levels of Cr and Pb. The metal sensitivity of the microbial community was determined by extracting bacteria from soil and measuring [(3)H]leucine incorporation as a function of metal concentration. Six soil samples collected in the spring of 1999 had IC(50) values (the heavy metal concentrations giving 50% reduction of microbial activity) of approximately 2.5 mM for CrO(4)2- and 0.01 mM for Pb2+. Much higher levels of Pb were required to inhibit [14C]glucose mineralization directly in soils. In microcosm experiments with these samples, microbial biomass and the ratio of microbial biomass to soil organic C were not correlated with the concentrations of hydrocarbons and heavy metals. However, microbial C respiration in samples with a higher level of hydrocarbons differed from the other soils no matter whether complex organic C (alfalfa) was added or not. The ratios of microbial C respiration to microbial biomass differed significantly among the soil samples (P < 0.05) and were relatively high in soils contaminated with hydrocarbons or heavy metals. Our results suggest that the soil microbial community was predominantly affected by hydrocarbons.
Selection of Phage-displayed Peptides Recognised by Monoclonal Antibodies Directed against the Lipopolysaccharide ofBrucella (2001)

Panning and screening of various phage display libraries with monoclonal antibodies (mAbs) directed against the O-chain of the lipopolysaccharide (LPS) of Brucella sp. allowed the identification of peptidic mimotopes of some O-chain epitopes. Four mAbs were tested. The A76-12G12 mAb, which is specific for LPS of all strains of Brucella, either A- or M-dominant, did not yield any peptidic mimotope, despite a specific yield enrichment during the rounds of panning. The B66-4F9 mAb, that recognises an epitope common to both Brucella sp. and Yersinia enterocilitca O:9 strains, allowed the selection of only one phage clone that was shown to be an antigenic but not immunogenic mimotope. The B66-2C8 and A15-6B3 mAbs, respectively, specific for the LPS of A-dominant and M-dominant Brucella sp., yielded several sequences, which allowed the determination of consensus sequences. These consensus will be of high interest for the construction of second generation libraries. For the best binding peptides, competition with LPS for the binding to the mAb is detected, which suggests that the peptides bind to the paratope of the mAb. The phages selected from the libraries were used to immunise mice, and a weak antibody response directed against LPS has been observed for some peptides. These data suggest that a subset of the selected peptides are immunogenic mimotopes of the LPS epitopes.
Effects of MDL 72527, a Specific Inhibitor of Polyamine Oxidase, on Brain Edema, Ischemic Injury Volume, and Tissue Polyamine Levels in Rats After Temporary Middle Cerebral After Occlusion (1999)

The possible effects of the polyamine interconversion pathway on tissue polyamine levels, brain edema formation, and ischemic injury volume were studied by using a selective irreversible inhibitor, MDL 72527, of the interconversion pathway enzyme, polyamine oxidase. In an intraluminal suture occlusion model of middle cerebral artery in spontaneously hypertensive rats, 100 mg/kg MDL 72527 changed the brain edema formation from 85.7 +/- 0.3 to 84.5 +/- 0.9% in cortex (p < 0.05) and from 79.9 +/- 1.7 to 78.4 +/- 2.0% in subcortex (difference not significant). Ischemic injury volume was reduced by 22% in the cortex (p < 0.05) and 17% in the subcortex (p < 0.05) after inhibition of polyamine oxidase by MDL 72527. There was an increase in tissue putrescine levels together with a decrease in spermine and spermidine levels at the ischemic site compared with the nonischemic site after ischemia-reperfusion injury. The increase in putrescine levels at the ischemic cortical and subcortical region was reduced by a mean of 45% with MDL 72527 treatment. These results suggest that the polyamine interconversion pathway has an important role in the postischemic increase in putrescine levels and that blocking of this pathway can be neuroprotective against neuronal cell damage after temporary focal cerebral ischemia.
Chemistry, Catalysts, and Processes for Isoparaffin–Olefin Alkylation: Actual Situation and Future Trends (1993)

Abstract As a consequence of the Clean Air Act (CAA), beginning in 1990, USA refiners were forced to change their strategy in order to meet the new mandatory specifications on gasoline composition. The targets established by the CAA were directed to overcoming environmental problems by reducing the ground-level ozone-forming and carbon monoxide emissions from vehicles, as well as toxic hydrocarbons and SO, and NO, emissions in auto exhausts. In order to accomplish this, gasolines had to move in the following direction: Reduce volatility: that is, lower Reid vapor pressure (RVP), especially during summer months, in order to reduce ozone levels. This can be achieved by removing butanes and even C, from the gasoline. Limitations in the aromatic content, with special emphasis on benzene. This can be solved by reducing reformate severity and/or by reducing the upper cut of the fluid catalytically cracked (FCC) gas-oline. Increased amount ofoxygenates, in which MTBE and TAME are preferred, especially in the carbon monoxide and ozone nonattainment areas. Reduction of olefins: This will be achieved by separating the C, olefins from FCC gasoline. Meanwhile, the elimination of C, olefins from the gasoline will further reduce RVP, and the isoamylenes will be used as a raw material to produce TAME in sterification units. Reduction of sulfur: Hydrotreating of FCC feeds, or hydrotreating or removing part of the heavy-end FCC gasoline. Elimination of lead: This, which was already under way when the new regulations were announced, produces a decrease in octane which has to be compensated by other streams coming into the gasoline pool.
Synchronous phase detection for optical fiber interferometric sensors (1983)

A system has been developed to accurately detect phase signals produced in optical interferometric sensors. The system employs optical heterodyning and synchronously detects optical phase by feeding back an error signal to a phase modulator in the reference leg of the interferometer. This system is seen to have properties similar to a phase-locked loop. The system is mathematically analyzed and a simple second-order model developed which accurately predicts the system response.
The Voltage-Gated Sodium Channel Na v 1.9 Is an Effector of Peripheral Inflammatory Pain Hypersensitivity (2006)

We used a mouse with deletion of exons 4, 5, and 6 of the SCN11A (sodium channel, voltage-gated, type XI, alpha) gene that encodes the voltage-gated sodium channel Na(v)1.9 to assess its contribution to pain. Na(v)1.9 is present in nociceptor sensory neurons that express TRPV1, bradykinin B2, and purinergic P2X3 receptors. In Na(v)1.9-/- mice, the non-inactivating persistent tetrodotoxin-resistant sodium TTXr-Per current is absent, whereas TTXr-Slow is unchanged. TTXs currents are unaffected by the mutation of Na(v)1.9. Pain hypersensitivity elicited by intraplantar administration of prostaglandin E2, bradykinin, interleukin-1beta, capsaicin, and P2X3 and P2Y receptor agonists, but not NGF, is either reduced or absent in Na(v)1.9-/- mice, whereas basal thermal and mechanical pain sensitivity is unchanged. Thermal, but not mechanical, hypersensitivity produced by peripheral inflammation (intraplanatar complete Freund's adjuvant) is substantially diminished in the null allele mutant mice, whereas hypersensitivity in two neuropathic pain models is unchanged in the Na(v)1.9-/- mice. Na(v)1.9 is, we conclude, an effector of the hypersensitivity produced by multiple inflammatory mediators on nociceptor peripheral terminals and therefore plays a key role in mediating peripheral sensitization.
Allele-selective inhibition of ataxin-3 (ATX3) expression by antisense oligomers and duplex RNAs (2011)

Spinocerebellar ataxia-3 (also known as Machado-Joseph disease) is an incurable neurodegenerative disorder caused by expression of a mutant variant of ataxin-3 (ATX3) protein. Inhibiting expression of ATX3 would provide a therapeutic strategy, but indiscriminant inhibition of both wild-type and mutant ATX3 might lead to undesirable side effects. An ideal silencing agent would block expression of mutant ATX3 while leaving expression of wild-type ATX3 intact. We have previously observed that peptide nucleic acid (PNA) conjugates targeting the expanded CAG repeat within ATX3 mRNA block expression of both alleles. We have now identified additional PNAs capable of inhibiting ATX3 expression that vary in length and in the nature of the conjugated cation chain. We can also achieve potent and selective inhibition using duplex RNAs containing one or more mismatches relative to the CAG repeat. Anti-CAG antisense bridged nucleic acid oligonucleotides that lack a cationic domain are potent inhibitors but are not allele-selective. Allele-selective inhibitors of ATX3 expression provide insights into the mechanism of selectivity and promising lead compounds for further development and in vivo investigation.
Development and comparison of molecular assays for the rapid detection of the pandemic influenza A (H1N1) 2009 virus (2010)

Human infection with the novel pandemic influenza A (H1N1) virus was first identified in April 2009. Two months later, the World Health Organization (WHO) had raised the pandemic level to phase 6. Rapid case identification is essential for prompt patient management and public health actions. This study developed real-time and conventional reverse transcription-polymerase chain reaction (rRT-PCR and cRT-PCR) assays for pandemic H1N1 detection, and compared their sensitivities with protocols developed by WHO reference centres. Altogether, three rRT-PCR and one cRT-PCR targeting the matrix gene for universal detection of influenza A; three rRT-PCR, one cRT-PCR targeting the hemagglutinin (HA) gene for specific detection of pandemic H1N1; and one multiplex cRT-PCR for differentiating co-circulating seasonal H1N1, H3N2, and pandemic H1N1 were examined. The lower detection limit ranged from 1.252 to 125.2 copy equivalents. In general, rRT-PCR assays were more sensitive than cRT-PCR assays. All assays showed 100% sensitivity for "optimal" specimens (nasopharyngeal samples collected within 4 days after illness onset). For the other 36 samples, cRT-PCR assays were less sensitive except that the new Protocol I-cRT-pdmH1 still retained 100% sensitivity. The new Protocol F-rRT-PCR-pdmH1 was the only pandemic virus-specific rRT-PCR assay with 100% sensitivity across all specimen categories. In conclusion, rRT-PCR assays are 10-fold more sensitive than cRT-PCR assays. The newly developed cRT-PCR assay targeting the HA gene allows rapid, specific, and sensitive screening of this novel agent, which can serve as an alternative for laboratories where a real-time PCR machine is not available.
Vitrification and levitation of a liquid droplet on liquid nitrogen (2010)

The vitrification of a liquid occurs when ice crystal formation is prevented in the cryogenic environment through ultrarapid cooling. In general, vitrification entails a large temperature difference between the liquid and its surrounding medium. In our droplet vitrification experiments, we observed that such vitrification events are accompanied by a Leidenfrost phenomenon, which impedes the heat transfer to cool the liquid, when the liquid droplet comes into direct contact with liquid nitrogen. This is distinct from the more generally observed Leidenfrost phenomenon that occurs when a liquid droplet is self-vaporized on a hot plate. In the case of rapid cooling, the phase transition from liquid to vitrified solid (i.e., vitrification) and the levitation of droplets on liquid nitrogen (i.e., Leidenfrost phenomenon) take place simultaneously. Here, we investigate these two simultaneous physical events by using a theoretical model containing three dimensionless parameters (i.e., Stefan, Biot, and Fourier numbers). We explain theoretically and observe experimentally a threshold droplet radius during the vitrification of a cryoprotectant droplet in the presence of the Leidenfrost effect.
Germination of Unactivated Spores ofBacillus cereusT (1976)

Heat-activated spores of Bacillus cereus T germinate rapidly in the presence of l-alanine alone or inosine alone. In contrast, unactivated spores can not germinate in the presence of either germinant alone but rapidly in the presence of both germinants. The highest level of cooperative action of l-alanine and inosine on the germination was observed when they were present in a ratio 1:1. Preincubations of unactivated spores with l-alanine or inosine had opposite effects on the subsequent germination in the presence of both germinants: preincubation with l-alanine stimulated the initiation of subsequent germination, while preincubation with inosine inhibited it. These results suggest that germination of unactivated spores initiated by l-alanine and inosine includes two steps, the first initiated by l-alanine and the second prompted by inosine. The effect of preincubation of unactivated spores with l-alanine was not diminished by washings. The pH dependence of the preincubation of unactivated spores was not so marked as that of the subsequent germination in the presence of inosine.
Iron-Catalyzed N-Alkylation of Azoles via Cleavage of an sp3C–H Bond Adjacent to a Nitrogen Atom (2012)

Iron-catalyzed direct C-N bond formation between azoles and amides is described. The oxidative coupling reactions of sp(3) C-H bonds adjacent to a nitrogen atom in amides and sulfonamides with the N-H bond in azoles proceeded smoothly in the presence of FeCl(2) and di-tert-butyl peroxide (DTBP).
Evolution and use of aluminum oxide single-tooth implant abutments: a short review and presentation of two cases. (2003)

The use of aluminum oxide ceramic abutments improves dental and mucogingival esthetics in single-implant restorations. The use of CAD/CAM technology simplifies the design and customization process. Clinical studies are required to confirm the long-term performance of this type of restoration.
Radiosensitization of malignant glioma cells through overexpression of dominant-negative epidermal growth factor receptor. (2001)

The epidermal growth factor receptor (EGFR) plays an important role in neoplastic growth control of malignant gliomas. We have demonstrated that radiation activates EGFR Tyr-phosphorylation (EGFR Tyr-P) and the proliferation of surviving human carcinoma cells, a likely mechanism of accelerated cellular repopulation, a major cytoprotective response after radiation. We now investigate the importance of radiation-induced activation of EGFR on the radiosensitivity of the human malignant glioma cells U-87 MG and U-373 MG. The function of EGFR was inhibited through a genetic approach of transducing cells with an Adenovirus (Ad) vector containing dominant-negative (DN) EGFR-CD533 (Ad-EGFR-CD533) at efficiencies of 85-90%. The resulting cells are referred to as U-87-EGFR-CD533 and U-373-EGFR-CD533. After irradiation at 2 Gy, both of the cell lines exhibited a mean 3-fold increase in EGFR Tyr-P. The expression of EGFR-CD533 completely inhibited the radiation-induced activation of EGFR. In clonogenic survival assays after a single radiation exposure, the radiation dose for a survival of 37% (D37) for U-87-EGFR-CD533 cells was 1.4- to 1.5-fold lower, relative to cells transduced with AdLacZ or untransduced U-87 MG cells. This effect was amplified with repeated radiation exposures (3 x 2 Gy) yielding a D37 ratio of 1.8-2.0. In clonogenic survival studies with U-373 MG cells, the radiosensitizing effect of EGFR-CD533 was similar. Furthermore, in vivo studies with U-87 MG xenografts confirmed the effect of EGFR-CD533 on tumor radiosensitization (dose enhancement ratio, 1.8). We conclude that inhibition of EGFR function via Ad-mediated gene transfer of EGFR-CD533 results in significant radiosensitization. As underlying mechanism, we suggest the disruption of a major cytoprotective response involving EGFR and its downstream effectors, such as mitogen-activated protein kinase. The experiments demonstrate for the first time that radiosensitization of malignant glioma cells through disruption of EGFR function may be achieved by genetic therapy approaches.