gebhart/patrepeval huggingface dataset:
Metabolic Engineering in Yeast Demonstrates ThatS-Adenosylmethionine Controls Flux through the Methylenetetrahydrofolate Reductase Reaction in Vivo (2002)

One-carbon flux into methionine and S-adenosylmethionine (AdoMet) is thought to be controlled at the methylenetetrahydrofolate reductase (MTHFR) step. Mammalian MTHFRs are inhibited by AdoMet in vitro, and it has been proposed that methyl group biogenesis is regulated in vivo by this feedback loop. In this work, we used metabolic engineering in the yeast Saccharomyces cerevisiae to test this hypothesis. Like mammalian MTHFRs, the yeast MTHFR encoded by the MET13 gene is NADPH-dependent and is inhibited by AdoMet in vitro. This contrasts with plant MTHFRs, which are NADH-dependent and AdoMet-insensitive. To manipulate flux through the MTHFR reaction in yeast, the chromosomal copy of MET13 was replaced by an Arabidopsis MTHFR cDNA (AtMTHFR-1) or by a chimeric sequence (Chimera-1) comprising the yeast N-terminal domain and the AtMTHFR-1 C-terminal domain. Chimera-1 used both NADH and NADPH and was insensitive to AdoMet, supporting the view that the C-terminal domain is responsible for AdoMet inhibition. Engineered yeast expressing Chimera-1 accumulated 140-fold more AdoMet and 7-fold more methionine than did the wild-type and grew normally. Yeast expressing AtMTHFR-1 accumulated 8-fold more AdoMet. This is the first in vivo evidence that the AdoMet sensitivity and pyridine nucleotide preference of MTHFR control methylneogenesis. (13)C labeling data indicated that glycine cleavage becomes a more prominent source of one-carbon units when Chimera-1 is expressed. Possibly related to this shift in one-carbon fluxes, total folate levels are doubled in yeast cells expressing Chimera-1.
Effects of Hydrogen on the Electronic Properties of Dilute GaAsN Alloys (2002)

Nitrogen has profound effects on the electronic structure of GaAs, as only a few percent of N can drastically lower the band gap. It is, however, not recognized that the same amount of N can also qualitatively alter the electronic behavior of hydrogen: First-principles calculations reveal that, in GaAsN, a H atom bonds to N and can act as a donor in its own right, whereas in GaAs and GaN, H is amphoteric, causing passivation instead. At high Fermi energy and H concentration, a N complex with two H was found to have lower energy than the single-H configuration. By removing the effect of N, this electrically inactive complex restores the gap of GaAs.
Knee Failure Mechanisms After Total Knee Arthroplasty (2004)

Total knee arthroplasty is a highly successful procedure, with the percentage of patients requiring revision relatively small. However, when considering the large number of these procedures performed annually, this small percentage of failures constitutes a significant number of patients. Failure of total knee arthroplasty is devastating to the patient, frustrating for the surgeon, and comes at a significant cost to the healthcare system. Therefore, it is imperative to understand the mechanisms of failure in knee arthroplasty. The leading causes include polyethylene wear, loosening, instability, and infection. It is important to recognize each mode of failure not only to appropriately diagnose and treat patients, but also to improve the future success of total knee arthroplasty.
The Modernisation of the Medieval Staging of Soul in Marlowe’s Doctor Faustus (2014)

For a play whose dramatic interest centers entirely on the fate of a man’s soul, Christopher Marlowe’s Doctor Faustus is curiously devoid of an attempt to reify its most central aspect, which is the soul itself. Unlike the medieval drama, which used a combination of linguistic, bodily and material devices to emblematize soul, in Doctor Faustus, the flow of meaning is reversed, and soul—having already been inculcated by centuries of religious teaching as the defining feature of humanity, to the point that no one in the play needs to ask, “what is the thing men call soul?”—is now used by Marlowe as the signature figure of poetical discourse on the seeming immutability of personal identity in the age of reformed theology. In Faustus, soul stands for one’s susceptibility to or potential for identity mutation, contrary to reigning systems of reward and punishment. The play foregrounds the way metaphorical language is used by a subject to articulate a dialectical relation between soul as a stage for the free play of the phenomenological events of an apperceptive mind, and soul as an anxiously situated, culturally conditioned identity.
An optimal viral peptide recognized by CD8+ T cells binds very tightly to the restricting class I major histocompatibility complex protein on intact cells but not to the purified class I protein. (1991)

CD8+ cytotoxic T lymphocytes recognize cell surface complexes formed by class I major histocompatibility complex (MHC-I) glycoproteins and antigenic peptides. We have identified a peptide nonamer (termed IV9) derived from the human immunodeficiency virus that is over a millionfold more active (at subpicomolar concentrations) than peptide analogues longer or shorter by one or two amino acid residues. Although IV9 does not detectably bind to isolated MHC-I molecules as measured by equilibrium dialysis, we quantitated its specific binding in unaltered form to MHC-I on intact cells. Less than 1% of cell surface MHC-I forms complexes with IV9, which suffices to trigger maximal cytotoxic T-lymphocyte activity. By contrast, a peptide dodecamer that includes the IV9 sequence and is active at micromolar concentrations does not bind to MHC-I on intact cells, raising the possibility that this longer peptide undergoes processing. Using stoichiometrically iodinated IV9 to obviate the ambiguities associated with trace labeling methods, we measured the dissociation kinetics of purified peptide/MHC-I complexes isolated by affinity chromatography and found these complexes to be exceedingly stable (t1/2 = 200-600 hr).
A Case of Profound Weight Loss Secondary to use of Reboxetine (2014)

Reboxetine is a selective norepinephrine re-uptake inhibitor used in the treatment of depression. The studies testing the effects of reboxetine on body weight have demonstrated that reboxetine reduces body weight and reboxetine found to be superior to placebo in reducing antipsychotic-induced weight gain. To date there are only a few cases in the literature of reboxetine use in adults resulting in profound weight loss. We present an unusual case report of a patient who experienced a marked weight loss with reboxetine treatment, regained weight after its withdrawal and experienced marked weight loss after re-challenge with reboxetine.
Peptide-Mediated Formation of Single-Wall Carbon Nanotube Composites (2005)

The formation of silica- and titania-coated single-wall carbon nanotubes (SWNTs) using a mutlifunctional peptide to both suspend SWNTs and direct the precipitation of silica and titania at room temperature is demonstrated.
Perivenous application of fibrin glue reduces early injury to the human saphenous vein graft wall in an ex vivo model (2002)

Fibrin glue is able to accomplish adequate external vein graft support, preventing overdistention, in an ex vivo model. This provides a basis for clinical application. Further investigation is necessary to evaluate long-term effects.
Quasicrystals and geometry (1995)

Preface 1. Past as prologue 2. Lattices, Voronoi cells, and quasicrystals 3. Introduction to diffraction geometry 4. Order on the line 5. Tiles and tilings 6. Penrose tilings of the plane 7. The aperiodic zoo 8. An atlas of tiling transforms Appendix I. A mathematician's toolbag Appendix II. De Bruijn's generalized functions References.
In vitro effects of heparin and tissue factor pathway inhibitor on factor VII assays. Possible implications for measurements in vivo after heparin therapy (2000)

The coagulant activity of blood coagulation factor VII (FVII:C) can be lowered by changes in lifestyle and by therapeutic intervention, e.g. heparin infusion. The question is, however, whether FVII:C determined ex vivo is a valid measure of the FVII activity in vivo. We measured plasma FVII:C, activated FVII (FVIIa), FVII protein (FVII:Ag), tissue factor pathway inhibitor (TFPI), triglycerides, and free fatty acids (FFA) before and 15 min after infusion of a bolus of unfractionated heparin (50 IU/kg body weight) in 12 healthy subjects. Additionally, we conducted in vitro experiments to investigate the effect of unfractionated heparin and TFPI, which is released from the endothelium by heparin, on FVII:C, FVIIa, and FVII:Ag. Heparin infusion decreased triglycerides and increased FFA and TFPI. This was accompanied by significant reductions in FVIIa, FVII:C and FVII:Ag. In vitro, anti-TFPI antibodies increased FVIIa and FVII:C, and heparin reduced FVIIa. The heparinase Hepzyme was unable to abolish the effect of heparin. There were no in vitro effects on FVII:Ag. We conclude that, due to interference by TFPI and heparin in post-heparin plasma, it is impossible to measure the in vivo FVII activity by means of FVII clotting assays. These assays should therefore not be used to measure the coagulation status of patients in heparin therapy, unless extraordinary precautions are taken to eliminate TFPI and heparin effects ex vivo. The observed effect of heparin on FVII:Ag should be investigated further.
Plasma Sheath Modeling in the Presence of Collisions (2002)

The present work develops a finite element discretized one-dimensional formulation for plasma-sheath dynamics, using multi-fluid equations. The applications include dc and rf sheath inside a glow discharge tube and a partially ionized plasma sheath inside a electric propulsion thruster channel. Based on the experimental data for multiple ionization of a noble gas, a third order polynomial has been used as a fit to describe ionization processes. Such a polynomial has been used to self-consistently calculate the rate of ionization in the plasma dynamic equations. The electron and ion number densities of the numerical solution decrease in the plasma-sheath region as expected. The ion velocity, sheath potential and electron temperature profiles also exhibit the expected behavior. The computed sheath potential compares well with the available experimental data. The model needs to be generalized in the near future for potential application to the high-speed air vehicles.
Sol-Gel Technology for Thin Films, Fibers, Preforms, Electronics and Specialty Shapes (1989)

This work covers principles, developments, and applications of sol-gel technology for thin films, fibers, preforms, electronics, and specialty shapes.
ERK-Dependent Downregulation of the Atypical Chemokine Receptor D6 Drives Tumor Aggressiveness in Kaposi Sarcoma (2014)

D6 is an atypical chemokine receptor acting as a decoy and scavenger for inflammatory CC chemokines expressed in lymphatic endothelial cells. Here, we report that D6 is expressed in Kaposi sarcoma (KS), a tumor ontogenetically related to the lymphatic endothelium. Both in human tumors and in an experimental model, D6 expression levels were inversely correlated with tumor aggressiveness and increased infiltration of proangiogenic macrophages. Inhibition of monocyte recruitment reduced the growth of tumors, while adoptive transfer of wild-type, but not CCR2(-/-) macrophages, increased the growth rate of D6-competent neoplasms. In the KS model with the B-Raf V600E-activating mutation, inhibition of B-Raf or the downstream ERK pathway induced D6 expression; in progressing human KS tumors, the activation of ERK correlates with reduced levels of D6 expression. These results indicate that activation of the K-Ras-B-Raf-ERK pathway during KS progression downregulates D6 expression, which unleashes chemokine-mediated macrophage recruitment and their acquisition of an M2-like phenotype supporting angiogenesis and tumor growth. Combined targeting of CCR2 and the ERK pathway should be considered as a therapeutic option for patients with KS.
Phylogenetic Diversity of Symbiotic Methanogens Living in the Hindgut of the Lower Termite Reticulitermes speratus Analyzed by PCR and In Situ Hybridization (1999)

A phylogenetic analysis of the sequences of 60 clones of archaeal small-subunit rRNA genes amplified from the termite Reticulitermes speratus revealed that most of them (56 clones) clustered in the genus Methanobrevibacter. Three clones were classified in the order Thermoplasmales. The Methanobrevibacter-related symbionts were detected by in situ hybridization analysis.
Integrin αvβ8 Functions as a Receptor for Foot-and-Mouth Disease Virus: Role of the β-Chain Cytodomain in Integrin-Mediated Infection (2004)

Field isolates of foot-and-mouth disease virus (FMDV) have been shown to use three alphav integrins, alphavbeta1, alphavbeta3, and alphavbeta6, as cellular receptors. Binding to the integrin is mediated by a highly conserved RGD motif located on a surface-exposed loop of VP1. The RGD tripeptide is recognized by several other members of the integrin family, which therefore have the potential to act as receptors for FMDV. Here we show that SW480 cells are made susceptible to FMDV following transfection with human beta8 cDNA and expression of alphavbeta8 at the cell surface. The involvement of alphavbeta8 in infection was confirmed by showing that virus binding and infection of the transfected cells are inhibited by RGD-containing peptides and by function-blocking monoclonal antibodies specific for either the alphavbeta8 heterodimer or the alphav chain. Similar results were obtained with a chimeric alphavbeta8 including the beta6 cytodomain (alphavbeta8/6), showing that the beta6 cytodomain can substitute efficiently for the corresponding region of beta8. In contrast, virus binding to alphavbeta6 including the beta8 cytodomain (alphavbeta6/8) was lower than that of the wild-type integrin, and this binding did not lead to infection. Further, the alphavbeta6 chimera was recognized poorly by antibodies specific for the ectodomain of alphavbeta6 and displayed a relaxed sequence-binding specificity relative to that of wild-type integrin. These data suggest that the beta6 cytodomain is important for maintaining alphavbeta6 in a conformation required for productive infection by FMDV.
Negative Regulation of the Forkhead Transcription Factor FKHR by Akt (1999)

The FKHR gene was first identified from its disruption by the t(2;13) chromosomal translocation seen in the pediatric tumor alveolar rhabdomyosarcoma. It encodes for a member of the forkhead family of transcription factors. Recently, a homolog of FKHR in the nematode Caenorhabditis elegans was identified called DAF-16, which is a downstream target of two Akt homologs in an insulin-related signaling pathway. We have examined the possible role of Akt in the regulation of FKHR. We find that FKHR can bind in vitro to the insulin-responsive sequence (IRS) in the insulin-like growth factor-binding protein 1 promoter and can activate transcription from a reporter plasmid containing multiple copies of the IRS. Expression of active but not inactive Akt can suppress FKHR-mediated transcriptional activation. Akt can phosphorylate FKHR in vitro on three phosphoacceptor sites, at least a subset of which can also be phosphorylated by Akt in vivo. Importantly, mutation of these three sites to alanine residues enhances the transcriptional activity of FKHR and renders it resistant to inhibition by Akt. Expression of an Akt-resistant mutant of FKHR causes apoptosis in 293T cells in a manner dependent on DNA binding. These results suggest that FKHR may be a direct nuclear regulatory target for Akt in both metabolic and cell survival pathways.
Expression of 12-lipoxygenase as a biomarker for melanoma carcinogenesis (2002)

12-Lipoxygenase (12-LOX), through its metabolite 12( )-hydroxyeicosatetraenoic acid [12( )-HETE], has been demonstrated to play a pivotal role in experimental melanoma invasion and metastasis, and 12-LOX expression may be important in early human melanoma carcinogenesis. We have studied the differences in 12-LOX protein expression during the progression of melanoma from human melanocytic cells to benign and dysplastic naevi to malignant metastatic disease. 12-LOX expression was determined in normal human skin melanocytes and in melanocytes found in compound naevi, dysplastic naevi and melanomas using a platelet-type 12-LOX antibody with a diaminobenzidine immunoperoxidase system detection system and was quantified using the analysis software NIH Image 1.62. Mean cellular pixel densities for 12-LOX staining ( = 50 cells/histological type) were unchanged in compound naevi ( = 0.14) and were increased in dysplastic naevi and melanomas compared with normal skin melanocytes ( = 0.03 and = 0.01, respectively). Similarly, melanomas had higher levels of expression compared with dysplastic naevi ( = 0.03). 12-LOX expression was significantly different between compound naevus and dysplastic naevus melanocytes ( = 0.01). These data suggest that 12-LOX may be an important novel marker for cancer progression within the melanoma system, and therefore could be a useful biomarker and therapeutic target for melanoma chemoprevention.
Antibody-based therapeutics in oncology (2003)

The recent clinical and commercial success of anticancer antibodies, such as rituximab (Rituxan) and trastuzumab (Herceptin) has created great interest in antibody-based therapeutics for hematopoietic malignancies and solid tumors. Given the likely lower toxicity for antibodies versus small molecules, the potential increase in efficacy by conjugation to radioisotopes and other cellular toxins and the ability to characterize the target with clinical laboratory diagnostics to improve the drug's clinical performance, it is anticipated that current and future antibody therapeutics will find substantial roles alone and in combination therapy strategies for the treatment of patients with cancer. It is also likely that conjugation strategies will add new radiolabeled and toxin-linked products to the market to complement the recent approvals of ibritumomab tiuxetan (Zevalin) and gemtuzumab ozogamycin (Mylotarg). However, although there are a large number of agents in both early and later stages of clinical development, only a handful will make it through regulatory approval and become successful products. This review considers the structure of anticancer therapeutic antibodies, the techniques used to reduce their antigenicity, factors that influence efficacy and toxicity, conjugation with isotopes and toxins and antibody target validation.
Military Space Activities: Highlights of the Rumsfeld Commission Report and Key Organization and Management Issues (2002)

This report discusses the Rumsfeld Commission's report and areas of concern within military space activities.
Current Protocols in Human Genetics (2018)

Abstract Cover: In Spector and Wiita. (http://doi.org/10.1002/cphg.106), the image shows a screenshot of ClinTAD's Single page for the example case. The top section of this page contains the input fields. The middle section contains an interactive visualization with several types of elements. These elements can include topologically associated domains (red), the copy number variant (green), genes with no phenotype matches (blue), genes with phenotype matches (orange), VISTA enhancers (purple), and DGV duplications (blue) and deletions (red). For the example case, both the MCTP2 (left side) and NR2F2 (right side) genes are highlighted in orange, indicating that they are associated with phenotypes that match to the patient. The last section of the page shows additional information for elements that are clicked on, in this case the MCTP2 gene.
IL-13 protects mice from lipopolysaccharide-induced lethal endotoxemia: correlation with down-modulation of TNF-alpha, IFN-gamma, and IL-12 production (1997)

IL-13 is a potent down-modulator of macrophage proinflammatory activity in vitro, similar in this context to the anti-inflammatory cytokines IL-4 and IL-10. Since IL-10 effectively confers protection to mice from LPS-induced lethal endotoxemia through inhibition of proinflammatory cytokine production, we investigated whether IL-13 may also be capable of providing protection in this experimental model of endotoxic shock. A single injection of recombinant murine IL-13 (rmIL-13; 0.5-10 microg) significantly increased survival in a dose-dependent manner when a lethal i.p. injection of endotoxin was administered to BALB/c mice. This effect appeared to be IL-13 specific, since survival was not affected in mice that received heat-inactivated rmIL-13. rmIL-13 provided significant protection to mice even when given 30 min after LPS injection; however, this protection decreased in a time-dependent manner as the administration of rmIL-13 was delayed by 1, 2, and 5 h following LPS injection. The protective effect of IL-13 was correlated with significant decreases in the production of the inflammatory mediators TNF-alpha, IFN-gamma, and IL-12 as well as a decrease in the anti-inflammatory mediator IL-10. Our data suggest that IL-13 provides protection from LPS-induced lethal endotoxemia in a manner that is similar to but independent from that of IL-10, and therefore can be added to the list of cytokine immunomodulators that might be beneficial in the treatment of septic shock.
Relationship Between Growth Rate, Cell Volume, Cell Cycle Kinetics, and Antigenic Properties of Cultured Murine Lymphoma Cells<xref ref-type="fn" rid="FN2">2</xref><xref ref-type="fn" rid="FN3">3</xref> (1970)

The expression of H-2 and Moloney leukemia virus (MLV)-determined surface antigens of MLV-induced mouse lymphoma cells (YCAB) was studied during growth in vitro by indirect membrane immunofluorescence and complement-dependent, antibody-mediated cytotoxic sensitivity. In a growing cell population, the degree of antigenic expression was inversely related to the growth rate and cell volume. These findings suggest that the antigenic properties of YCAB cells are maximally expressed during the early interphase, presumably a part of the G1 period, and that the fast-growing cells pass relatively quickly through G1. The life cycle analysis of the same cells at varying intervals during the growth cycle revealed that the prolongation of population doubling time was mainly due to an extension of the G1 period, whereas the duration of S, G2, and mitosis was much less affected. The cell volume per se did not appreciably influence the expression of surface antigens. Populations of large cells were more rapidly growing, since they were in the late stage of their cycle.
CTLs are targeted to kill β cells in patients with type 1 diabetes through recognition of a glucose-regulated preproinsulin epitope (2008)

The final pathway of beta cell destruction leading to insulin deficiency, hyperglycemia, and clinical type 1 diabetes is unknown. Here we show that circulating CTLs can kill beta cells via recognition of a glucose-regulated epitope. First, we identified 2 naturally processed epitopes from the human preproinsulin signal peptide by elution from HLA-A2 (specifically, the protein encoded by the A*0201 allele) molecules. Processing of these was unconventional, requiring neither the proteasome nor transporter associated with processing (TAP). However, both epitopes were major targets for circulating effector CD8+ T cells from HLA-A2+ patients with type 1 diabetes. Moreover, cloned preproinsulin signal peptide-specific CD8+ T cells killed human beta cells in vitro. Critically, at high glucose concentration, beta cell presentation of preproinsulin signal epitope increased, as did CTL killing. This study provides direct evidence that autoreactive CTLs are present in the circulation of patients with type 1 diabetes and that they can kill human beta cells. These results also identify a mechanism of self-antigen presentation that is under pathophysiological regulation and could expose insulin-producing beta cells to increasing cytotoxicity at the later stages of the development of clinical diabetes. Our findings suggest that autoreactive CTLs are important targets for immune-based interventions in type 1 diabetes and argue for early, aggressive insulin therapy to preserve remaining beta cells.