gebhart/patrepeval huggingface dataset:
Inhibition of viral mRNA translation in interferon-treated L cells infected with reovirus (1985)

Murine L cells were treated with interferon (IFN) concentrations which reduced by 75 to 80% the synthesis of viral mRNA after infection with reovirus. Protein synthesis was not inhibited in these cells up to 6 h after infection, but a large fraction of the viral mRNA was not associated with polyribosomes and sedimented at about 50S. In contrast, most of the reovirus mRNA was associated with polyribosomes in control infected cells. This mRNA was of similar size to non-polyribosomal mRNA from IFN-treated cells when analyzed by Northern blot hybridization with a cloned cDNA for the s2 reovirus mRNA, indicating that the non-polyribosomal mRNA was not appreciably degraded. Viral mRNA was labeled with [3H]uridine and the non-polyribosomal mRNA was isolated from IFN-treated cells. This mRNA could quantitatively bind to 80S initiation complexes when incubated in a rabbit reticulocyte cell-free system. These findings indicated that the non-polyribosomal RNA was translatable, but that its binding to functional initiation complexes was inhibited in IFN-treated cells by a discriminatory mechanism, which did not affect translation of cellular mRNA. Previous experiments showed that mRNA is blocked in 48S complexes when the alpha subunit of initiation factor eIF-2 is phosphorylated by the double-stranded RNA-dependent protein kinase induced by IFN. A localized activation of this kinase could explain the block of viral mRNA in 48S complexes. By labeling the phosphoproteins of IFN-treated cells with 32P, eIF-2 (alpha P) was shown to cosediment with non-polyribosomal mRNA, presumably in 48S complexes.
Regulatory mechanisms for production of IFN-gamma and TNF by antitumor T cells or macrophages in the tumor-bearing state. (1995)

Spleen cells from BALB/c mice bearing a syngeneic tumor (CSA1 M) 2 to 3 wk after inoculation with CSA1 M cells produced IL-2, IFN-gamma, and TNF upon in vitro cultures. This was previously demonstrated to be a result of collaboration between tumor-primed CD4+ T cells and APCs binding CSA1 M tumor Ags in vivo. The IL-2- and IFN-gamma-producing capacities decreased with the progress of tumor-bearing stages. This was parallel to the levels of IL-2 and IFN-gamma mRNAs expressed by cultured spleen cells. In contrast, comparable levels of TNF mRNA were expressed by all groups of cultured cells. However, large amounts of TNF were secreted by the cells from early but not from late tumor-bearing mice. TNF was produced mainly by the non-T cell fraction upon stimulation with CD4+ T cell-derived IFN-gamma. Therefore, the reduced TNF production by whole spleen cells from late tumor-bearing mice was restored by addition of rIFN-gamma to their cultures. Reciprocally to the progressive decrease in the production of IFN-gamma/TNF, the capacities of tumor-bearing mice to produce TGF-beta and IL-6 increased along with tumor growth. TGF-beta suppressed production of IL-2, IFN-gamma, and TNF, but not of IL-6. Moreover, IFN-gamma/TNF production was negatively regulated by IL-6. Taken together with the fact that the growth of CSA1 M cells is completely inhibited by the combination of TNF and IFN-gamma, these results demonstrate that the tumor-bearing state induces an abnormal cytokine network under which the production of antitumor cytokines is negatively regulated.
A monoclonal anti-human plasma prekallikrein antibody that inhibits activation of prekallikrein by factor XIIa on a surface (1987)

Abstract Of five IgGI/k murine monoclonal anti-human prekallikrein antibodies produced (MAbs), MAb 13G11 was selected for studying interaction of prekallikrein with factor XII and high-mol-wt kininogen (HMWK) during activation on a surface. Immunoblots from sodium dodecyl sulfate (SDS) gels showed that this MAb recognizes two variants (88 kd and 85 kd) of prekallikrein and kallikrein both in purified proteins and normal plasma. Under reducing conditions, kallikrein exhibits the epitope on the heavy chain but not on the light chains. Preincubation of MAb 13G11 with prekallikrein (added to prekallikrein-deficient plasma) or with normal plasma inhibited surface activation of prekallikrein 60% to 80%, as judged by amidolytic and coagulant assays. In normal plasma, inhibition by the Fab fragments was 87% of that with the entire MAb. Inhibition was not by competition between the MAb and HMWK, since neither binding of 13G11 to prekallikrein (coated on microtiter plates) was inhibited by an excess of HMWK, nor was hydrolysis of HMWK by kallikrein inhibited by 13G11. Using purified proteins in a system mimicking contact activation, inhibition by 13G11 of prekallikrein activation by factor XIIa, HMWK, and kaolin present was approximately 80%. Decreased inhibition (55% to 25%) occurred without HMWK or when kallikrein was used instead of prekallikrein. Kallikrein activity was not inhibited by 13G11 Fab fragments. These results indicate that the effect of 13G11 in plasma was neither dissociation of prekallikrein- HMWK complex nor a direct effect on kallikrein activity. Similar to the results in plasma, activation of prekallikrein, HMWK present, by factor XIIa bound to kaolin, was inhibited approximately 70% by 13G11. The results suggest a previously unrecognized site on the prekallikrein (heavy chain) required for its interaction with factor XIIa, either shared with the 13G11 epitope or located in very close proximity. The inhibition of kallikrein by intact 13G11 indicates that its binding site on the heavy chain is sterically related to the active site (light chain).
Microprobe characterization of sputtered high Tc superconducting films on silicon (1988)

High Tc superconducting thin films on silicon substrates were prepared and characterized. Thin films were deposited by RF diode sputtering from a single compound target. Microprobe anlysis using Auger Electron Spectroscopy (AES), Scanning Electron Microscopy (SEM) and Energy Dispersive X‐Ray Spectrometry (EDXS) was used to characterize the structure and the composition. A severe interaction between the silicon substrate and the film was observed. A sputtered zirconium oxide film was studied as an interdiffusion barrier on the silicon substrate. The best film on Si with a ZrO2 barrier layer has Tc (midpoint)=88K and transition width=8K with some tail.
Synthesis of hydroxy- and amino-substituted benzohydroxamic acids: inhibition of ribonucleotide reductase and antitumor activity (1979)

Benzohydroxamic acids inhibit mammalian ribonucleotide reductase and exhibit antineoplastic activity in L1210 leukemic mice. Five new hydroxy- and amino-substituted benzohydroxamic acids (3,4- and 3,5-OH, 3,4-NH2, 2,3,4- and, 3,4,5-OH) were prepared and tested along with 12 previously reported benzohydroxamic acids (BHA) for enzyme inhibition and antitumor activity. The most potent enzyme inhibitor in this series was 2,3,4-OH-BHA (ID50 = 3.5 microM), which is 140 times more potent than hydroxyurea, but its toxicity limited the antitumor activity to a 30% increase in life span of L1210 bearing mice at 125 (mg/kg)/day ip for 8 days. The most effective antitumor agent in this series was 3,4-OH-BHA which prolonged the life span of L1210 bearing mice 103% at 600 (mg/kg)/day ip for 8 days.
Highly efficient 4-W Yb-doped fiber amplifier pumped by a broad-stripe laser diode (1999)

A Yb-doped double-cladding fiber amplifier is v-groove side pumped by a 100-microm -wide, broad-stripe, 975-nm laser diode. The amplifier exhibits, separately, 39% electrical-to-optical conversion efficiency, 89% internal optical-to-optical conversion efficiency, 4-W output power at 1060 nm, and a small-signal gain of 53 dB.
Vascular endothelial growth factor (VEGF‐A) expression in human mesenchymal stem cells: Autocrine and paracrine role on osteoblastic and endothelial differentiation (2005)

Angiogenesis is essential in bone fracture healing for restoring blood flow to the fracture site. Vascular endothelial growth factor (VEGF) and its receptor have been implicated in this process. Despite the importance of angiogenesis for the healing processes of damaged bones, the role of VEGF signaling in modulation of osteogenic differentiation in human mesenchymal stem cells has not been investigated in great detail. We examined the expression of VEGF-A and VEGFR-1 in human adult mesenchymal stem cells derived from trabecular bone (hTBCs). VEGF-A was found to be secreted in a differentiation dependent manner during osteogenesis. Transcripts for VEGF-A were also seen to be elevated during osteogenesis. In addition, transcripts for VEGF-A and the corresponding receptor VEGFR-1 were upregulated under hypoxic conditions in undifferentiated hTBCs. To investigate the signaling of VEGF-A on osteogenesis recombinant hTBCs were generated. High expression of VEGF-A stimulated mineralization, whereas high expression of sFLT-1, an antagonist to VEGF-A, reduced mineralization suggesting that VEGF-A acts as autocrine factor for osteoblast differentiation. In addition, VEGF-A secreted by hTBCs promotes sprouting of endothelial cells (HUVE) demonstrating a paracrine role in blood vessel formation. In summary, an in vitro analysis of transgene effects on cellular behavior can be used to predict an effective ex vivo gene therapy.
Kinetic and Pharmacological Properties of Cloned Human Equilibrative Nucleoside Transporters, ENT1 and ENT2, Stably Expressed in Nucleoside Transporter-deficient PK15 Cells (2000)

We stably transfected the cloned human equilibrative nucleoside transporters 1 and 2 (hENT1 and hENT2) into nucleoside transporter-deficient PK15NTD cells. Although hENT1 and hENT2 are predicted to be 50-kDa proteins, hENT1 runs as 40 kDa and hENT2 migrates as 50 and 47 kDa on SDS-polyacrylamide gel electrophoresis. Peptide N-glycosidase F and endoglycosidase H deglycosylate hENT1 to 37 kDa and hENT2 to 45 kDa. With hENT1 being more sensitive, there is a 7000-fold and 71-fold difference in sensitivity to nitrobenzylthioinosine (NBMPR) (IC(50), 0.4 +/- 0.1 nM versus 2.8 +/- 0.3 microM) and dipyridamole (IC(50), 5.0 +/- 0.9 nM versus 356 +/- 13 nM), respectively. [(3)H]NBMPR binds to ENT1 cells with a high affinity K(d) of 0.377 +/- 0.098 nM, and each ENT1 cell has 34,000 transporters with a turnover number of 46 molecules/s for uridine. Although both transporters are broadly selective, hENT2 is a generally low affinity nucleoside transporter with 2.6-, 2.8-, 7. 7-, and 19.3-fold lower affinity than hENT1 for thymidine, adenosine, cytidine, and guanosine, respectively. In contrast, the affinity of hENT2 for inosine is 4-fold higher than hENT1. The nucleobase hypoxanthine inhibits [(3)H]uridine uptake by hENT2 but has minimal effect on hENT1. Taken together, these results suggest that hENT2 might be important in transporting adenosine and its metabolites (inosine and hypoxanthine) in tissues such as skeletal muscle where ENT2 is predominantly expressed.
Thermodynamic and kinetic characterization of the dissociation and assembly of quadruplex nucleic acids (2000)

The dissociation and assembly of quadruplex DNA structures (and a few quadruplex RNAs) have been characterized at several levels of rigor, ranging from gross descriptions of factors that govern each process, to semiquantitative comparisons of the relative abilities of these factors to induce stabilization or destabilization, to quantitative studies of binding energies (thermodynamics), transformational rates (kinetics), and analysis of their transition-state energies and mechanisms. This survey classifies these factors, describes the trends and focuses on their interdependencies. Quadruplex assembly is induced most efficiently by added K(+) and elevating the strand concentration; however, Na(+), NH(4)(+), Sr(2+), and Pb(2+) are also very effective stabilizers. Quadruplex dissociation is typically accomplished by thermal denaturation, "melting"; however, when the quadruplex and monovalent cation concentrations are low enough, or the temperature is sufficiently high, several divalent cations, e.g., Ca(2+), Co(2+), Mn(2+), Zn(2+), Ni(2+) and Mg(2+) can induce dissociation. Stabilization also depends on the type of structure adopted by the strand (or strands) in question. Variants include intramolecular, two- and four-stranded quadruplexes. Other important variables include strand sequence, the size of intervening loops and pH, especially when cytosines are present, base methylation, and the replacement of backbone phosphates with phosphorothioates. Competitive equilibria can also modulate the formation of quadruplex DNAs. For example, reactions leading to Watson-Crick (WC) duplex and hairpin DNAs, triplex DNAs, and even other types of quadruplexes can compete with quadruplex association reactions for strands. Others include nonprotein catalysts, small molecules such as aromatic dyes, metalloporphyrins, and carbohydrates (osmolytes). Other nucleic acid strands have been found to drive quadruplex formation. To help reinforce the implications of each piece of information, each functional conclusion drawn from each cited piece of thermodynamic or kinetic data has been summarized briefly in a standardized table entry.
Modulation of cholinergic and substance P‐like neurotransmission by nitric oxide in the guinea‐pig ileum (1993)

1. The role of endogenous nitric oxide (NO) as a modulator of enteric neurotransmission was investigated in longitudinal muscle myenteric plexus (LMMP) preparations of guinea-pig isolated ileum. 2. In tissues previously incubated with [3H]-choline, exogenous NO inhibited electrically-evoked [3H]-choline overflow as well as responses to exogenous agonists, indicating that NO has the potential of neuromodulation both pre- and postjunctionally. 3. A series of NO synthase inhibitors enhanced contractile responses to nerve stimulation indicating inhibitory neuromodulation by endogenous NO. 4. The potency order of the NO synthase inhibitors and their consistent effects after dexamethasone, on responses to nerve stimulation, indicate action on a constitutive NO synthase. 5. Responses enhanced by NO synthase inhibitors were inhibited by the substance P receptor antagonist, spantide, suggesting a neuromodulatory influence on substance P-like neurotransmission by the endogenous NO. 6. NO synthase inhibition did not modify contractile responses to application of acetylcholine or substance P, or [3H]-choline overflow, indicating that endogenous NO mainly has a prejunctional inhibitory action on substance P-like neurotransmission. Nor did it modify responses to direct electrical muscle stimulation in the presence of tetrodotoxin. This suggests a prejunctional enhancing effect by NO synthesis inhibition. 7. Evidence for endogenous NO modulation of acetylcholine release was obtained when NO synthase inhibition modified atropine-sensitive, nerve-mediated contractile responses. However, [3H]-choline overflow was unaltered by NO synthase inhibition. 8. NO synthase inhibition did not modify responses to inhibitory neurotransmission. 9. The findings suggest that endogenous NO inhibits substance P-like motor neurotransmission, probably via prejunctional mechanisms. Cholinergic transmission may also be reduced by endogenous NO, acting prejunctionally.
Sojourn times in non-homogeneous QBD processes with processor sharing (1999)

We study sojourn times of customers in a processor sharing model with a service rate that varies over time, depending on the number of customers and on the state of a random environment. An explicit expression is derived for the Laplace-Stieltjes transform of the sojourn time conditional on the state upon arrival and the amount of work brought into the system. Particular attention is given to the conditional mean sojourn time of a customer as a function of his required amount of work, and we establish the existence of an asymptote as the amount of work tends to infinity. The method of random time change is then extended to include the possibility of a varying service rate. By means of this method, we explain the well-established proportionality between the conditional mean sojourn time and required amount of work in processor sharing queues without random environment. Based on numerical experiments, we propose an approximation for the conditional mean sojourn time. Although first prese...
Antimicrobial resistance: the example of Staphylococcus aureus (2003)

methicillin-resistant Staphylococcus aureus (MRSA); staphylococcal cassette chromosome mec (SCCmec); methicillin-susceptible S. aureus (MSSA
Human Responses to Exercise-Heat Stress (1993)

This report provides a comprehensive overview of the normal human physiological responses to environmental and exercise-related heat stress, with emphasis placed on acute heat exposure and acclimation produced by repeated heat exposure. In addition, the report reviews biomedical factors that modify exercise-heat tolerance such as aerobic fitness, dehydration, circadian patterns and sleep loss and medications. Also, the report reviews thermoregulatory responses of special populations such as women, blacks, children, older adults and spinal cord injured populations. Temperature Regulation, Body temperature, Heat stress, Heat loss, Sweating, Skin blood flow
Interleukin 1 receptor antagonist mediates the antiinflammatory and antifibrotic effect of mesenchymal stem cells during lung injury (2007)

Mesenchymal stem cells (MSCs) have been exploited as cellular vectors to treat a wide array of diseases but the mechanisms responsible for their therapeutic effect remain indeterminate. Previously, we reported that MSCs inhibit bleomycin (BLM)-induced inflammation and fibrosis within the lungs of mice. Interrogation of the MSC transcriptome identified interleukin 1 receptor antagonist (IL1RN) as a potential mediator of this effect. Fractionation studies indicated that MSCs are the principal source of IL1RN in murine bone marrow and that its expression is restricted to a unique subpopulation of cells. Moreover, MSC-conditioned media was shown to block proliferation of an IL-1α-dependent T cell line and inhibit production of TNF-α by activated macrophages in vitro . Studies conducted in mice revealed that MSC administration was more effective than recombinant IL1RN delivered via adenoviral infection or osmotic pumps in inhibiting BLM-induced increases in TNF-α, IL-1α, and IL1RN mRNA in lung, IL1RN protein in bronchoalveolar lavage (BAL) fluid, and trafficking of lymphocytes and neutrophils into the lung. Therefore, MSCs protect lung tissue from BLM-induced injury by blocking TNF-α and IL-1, two fundamental proinflammatory cytokines in lung. Identification of IL1RN-expressing human MSC subpopulations may provide a novel cellular vector for treating chronic inflammatory diseases in humans.
Bcl-2 protein expression and long-term survival in breast cancer. (1994)

Bcl-2 gene product functions to prevent apoptosis in a variety of in vitro and in vivo experiments. The prognostic significance of Bcl-2 protein expression was investigated by immunocytochemistry from paraffin-embedded tissue in a series of 174 women with breast cancer, treated with radical surgery with or without regional radiotherapy, and who had been followed up for the median of 31 years or until death. A minority (25%) of cancers were entirely negative for Bcl-2 protein. Moderate to strong Bcl-2 protein expression (present in 46%) was strongly associated with several favorable prognostic features, such as a low mitotic count, high histological grade of differentiation, and lack of p53 protein expression (P < 0.0001 for each). It was also significantly associated with lack of tumor necrosis, a low S-phase fraction size, low cathepsin D expression, DNA diploidy, and the lobular histological type, but not with the primary tumor size or the axillary nodal status. Women with cancer with moderate to strong Bcl-2 protein expression had more favorable short-term (69% versus 46% alive at 5 years) but similar long-term (29% versus 33% alive at 30 years) disease-specific survival as those with cancer with weak or lacking expression. Bcl-2 protein expression did not have independent prognostic value in a multivariate survival analysis. We conclude that Bcl-2 protein is frequently expressed in breast cancer, and its expression is associated with favorable clinicopathological features.
The relationship between low density lipoprotein-related protein/alpha 2-macroglobulin (alpha 2M) receptors and the newly described alpha 2M signaling receptor (1994)

alpha 2-Macroglobulin (alpha 2M)-methylamine binding to macrophages appears to involve two receptors. Binding of alpha 2M-methylamine to low density lipoprotein-related protein (LRP) results in cellular uptake and degradation, while binding to a newly described alpha 2M signaling receptor elevates intracellular calcium ([Ca2+]i) and inositol phosphates. We now demonstrate that binding of lactoferrin, Pseudomonas exotoxin A, and lipoprotein lipase to LRP on macrophages results in increased [Ca2+]i and inositol 1,4,5-triphosphate. Receptor-associated protein, which binds to LRP but not the alpha 2M signaling receptor, blocks the lactoferrin signal but has no effect on alpha 2M-methylamine signaling. The latter observation supports our hypothesis that a distinct signaling receptor binds alpha 2M-methylamine. We further demonstrate that the signaling events induced by lactoferrin may involve a pertussis toxin-sensitive G protein, while the alpha 2M signaling receptor appears to be coupled to a pertussis toxin-insensitive G protein.
Restoration of thalamostriatal projections in rat neostriatal grafts: An electron microscopic analysis (1991)

The thalamostriatal projections to rat neostriatal grafts were studied by using the Phaseolus vulgaris-leucoagglutinin (PHA-L) axonal tracing technique. Two to 6 months after implantation of striatal primordia into adult neostriata, PHA-L was injected into two different portions of the intralaminar nuclear complex of the thalamus. In the host neostriatum, labeled fibers from the parafascicular nucleus (PF) arborized in a large region in the neostriatum, but avoided small patchlike areas. Most of the fibers from PF had irregular curved trajectories with short side branches that formed boutons. Labeled fibers from the centromedial and paracentral nuclei (CeM-PC) projected to a similarly large area within the neostriatum but did not show any nonuniformity. CeM-PC axons had relatively straight trajectories and formed boutons en passant. Both sets of thalamostriatal projection fibers were found in the grafts. Some of the labeled fibers in the grafts formed dense, focal arborizations. Compared to the host neostriatum, the distribution of postsynaptic elements in the grafts was altered dramatically. In the host neostriatum, 89% of the terminals from PF terminated onto dendritic shafts; 93% of the CeM-PC terminals contacted dendritic spines. However, only 47% of the PF terminals in the grafts contacted dendritic shafts; 53% of them terminated on dendritic spines. In grafts, 81% of the terminals from CeM-PC region contacted dendritic spines; 19% of them made synapses on dendritic shafts. The shift of postsynaptic elements in the grafts suggests a loss of pathway specificity in the induction of dendritic spines on neostriatal neurons in grafts.
Spin-dependent magnetotransport in a p-InMnSb/n-InSb magnetic semiconductor heterojunction (2011)

The spin-dependent transport properties in p-InMnSb/n-InSb magnetic semiconductor heterojunctions are presented. A positive junction giant magnetoresistance is observed from 75 to 298 K. The magnetoresistance is attributed to conduction via two spin channels resulting from p-d exchange interaction. The magnetoconductance of the heterojunction and its magnetic field dependence are well-described by a two-band model where the bands are spin-polarized. At 75 K and zero field, the spin polarization in the alloy is 90% and decreases to 48% at 298 K. The large spin polarization indicates that InMnSb should be suitable for spin-based transistors that operate at room temperature.