gebhart/patrepeval huggingface dataset:
Time Travel (1992)

To travel into the past, to observe it, perhaps to influence it and correct mistakes of one's youth, has been an abiding fantasy of mankind for as long as we have been aware of a past. Here are described some recent scientific investigations on this topic.
Induction of Phosphoglycerate Kinase 1 Gene Expression by Hypoxia (1996)

To identify new dimerization partners for the aromatic hydrocarbon receptor nuclear translocator (Arnt), we used its N-terminal region (amino acids 1-470) as a target in a two-hybrid screening procedure, and we cloned the murine form of hypoxia-inducible factor 1alpha (HIF1alpha). Sequence comparisons reveal substantial identity between mouse and human HIF1alpha. Hypoxia induces a 10-fold accumulation of phosphoglycerate kinase 1 mRNA in wild type mouse hepatoma (Hepa 1c1c7) cells; the induction mechanism is Arnt dependent because induction does not occur in Arnt-defective cells. Furthermore, induction of phosphoglycerate kinase 1 mRNA requires Arnt's N-terminal region, which mediates DNA binding and heterodimerization; in contrast, induction does not require Arnt's C-terminal region, which mediates transactivation. We also show that a GAL4-HIF1alpha fusion protein transactivates a GAL4-dependent gene in the absence of Arnt, that HIF1alpha's transactivation capability is inducible by hypoxia, and that both hypoxia responsiveness and transactivation capability reside within the C-terminal 83 amino acids of HIF1alpha. Our findings generate new insights into the mechanism by which Arnt and HIF1alpha induce transcription in response to hypoxia.
Reliance on external cues during serial sequential movement in major depression (2000)

Maintenance of motor set in patients with unipolar major depression was examined. Twelve melancholic and 12 non-melancholic depressed patients and 24 age matched controls performed a serial choice reaction time task while external cues aiding maintenance of a motor set were systematically removed. Melancholic patients were significantly slower than controls with no reduction in external cues and with a moderate reduction in external cues. At a high level of reduction in external cues, seven of 12 melancholic patients (but only three of 12 non-melancholic patients and controls) were unable to complete the task; suggesting a greater reliance on external cues, perhaps implicating a failure of motor planning ability in melancholic patients. This, in turn, may point to a prefrontal (premotor) deficit in melancholic depression, with possible commonalities with Parkinson's disease.
Repetitive A epitope (type 3 chain A) defined by blood group A1-specific monoclonal antibody TH-1: chemical basis of qualitative A1 and A2 distinction. (1985)

The IgG2a monoclonal antibody TH-1, which reacts specifically with blood group A1 but with neither A2 nor O erythrocytes, has been established. The antibody reacted only with A1 erythrocytes in hemagglutination and antibody absorption assays; it did not react with A2 erythrocytes, even after trypsin or sialidase treatment. This antibody detected, on TLC immunostaining, a series of glycolipids from A1 erythrocytes but virtually none or very weak bands from A2 erythrocytes. It did not react with type 1 or type 2 chain A, or with globo-A. The simplest reactive component was isolated from a previously assigned Ab fraction by HPTLC of acetylated compounds. The structure of the reactive component was characterized by 1H NMR spectroscopy, methylation analysis, and enzymatic degradation, as shown below: (Formula: see text). The structure is essentially a repetitive A epitope attached to type 2 chain and is hereby called type 3 chain A. The determinant can be carried on extended and/or branched structures, but it was not detectable in glycoproteins. The structure was characteristic of A1 erythrocytes and present in only trace amounts in A2 erythrocytes. The precursor H (Fuc alpha 1----2Gal beta 1----3GalNAc alpha 1----3[Fuc alpha 1----2]Gal beta 1----4GlcNAc beta 1----R; type 3 chain H) was present in greater quantity in A2 erythrocytes than in A1 erythrocytes, but it was absent in both O and B erythrocytes. The A1 transferase apparently can transfer alpha-GalNAc to type 3 chain H, while the A2 transferase may not have this ability.
A Ring-Opening Metathesis Polymerization (ROMP) Approach to Carboxyl- and Amino-Terminated Telechelic Poly(butadiene)s (2000)

Over the past several years there has been an increasing interest in the synthesis of polymers with low glass transition temperatures and reactive functional groups at each end of a given polymeric chain. They have found use as agents capable of modifying the thermal and mechanical properties of condensation polymers, in the formation of polymeric networks, and as components in the synthesis of block copolymers. Telechelic hydroxyl, amino, and carboxyl poly(butadiene)s (PBD)s are excellent examples of such polymers that have been employed in the above applications. While these telechelic polymers can be synthesized through the radical or anionic polymerization of 1,3-butadiene using the appropriate initiating or terminating agents, there are several drawbacks. The average number of functional groups per polymer chain (F_n) can deviate greatly from 2 and depends heavily on experimental conditions, which are often demanding. Furthermore, varying amounts of 1,2-linkages are introduced during the polymerization, limiting the elastomeric potential of the resulting polymer.
DNA unwinding upon strand-displacement binding of a thymine-substituted polyamide to double-stranded DNA. (1993)

It was recently found that polyamide nucleic acid (PNA) analogues consisting of thymines attached to an aminoethylglycine backbone bind strongly and sequence-selectively to adenine sequences of oligonucleotides and double-stranded DNA [Nielsen, P. E., Egholm, M., Berg, R. H. & Buchardt, O. (1991) Science 254, 1497-1500]. It was concluded that the binding to double-stranded DNA was accomplished via strand displacement, in which the PNA bound to the Watson-Crick complementary adenine-containing strand, whereas the thymine-containing strand was extruded in a virtually single-stranded conformation. This model may provide a general way in which to obtain sequence-specific recognition of any sequence in double-stranded DNA by Watson-Crick hydrogen-bonding base-pair recognition, and it is thus paramount to rigorously establish this binding mode for synthetic DNA-binding ligands. We now report such results from electron microscopy. Furthermore, we show that binding of PNA to closed circular DNA results in unwinding of the double helix corresponding to approximately one turn of the double helix per 10 base pairs. The DNA.PNA complex, which is formed at low salt concentration (only a small portion of DNA molecules show complex formation at NaCl concentration higher than 40 mM), is exceptionally kinetically stable and cannot be dissociated by increasing salt concentration up to 500 mM.
Activated STAT3 is a mediator and biomarker of VEGF endothelial activation (2008)

STAT3 plays important roles in cell proliferation and survival signaling and is often constitutively activated in transformed cells. In this study, we examined STAT3 activation in endothelial cells (EC) during angiogenic activation and therapeutic angiogenesis inhibition. VEGF stimulation of cultured EC induced STAT3 phosphorylation by a VEGFR2- and Src-dependent mechanism. FGF2 but not PlGF also induced EC STAT3 activation in vitro. Activated STAT3 mediated VEGF induction of EC Bcl-2 and contributed to VEGF protection of EC from apoptosis. In vivo, p-STAT3 was absent by immunohistological staining in the vascular EC of most normal mouse organs but was present in the vessels of mouse and human tumors. Tumor vascular p-STAT3 increased as tumors were induced to overexpress VEGF, indicating that VEGF is an activator of EC p-STAT3 in vivo. Tumor vascular p-STAT3 decreased during angiogenesis inhibition by antagonists of VEGF-VEGFR signaling, VEGF Trap and SU5416, indicating that VEGF contributed to the EC STAT3 activation seen in the tumors prior to treatment and that p-STAT3 may be used to monitor therapy. These studies show that p-STAT3 is a mediator and biomarker of endothelial activation that reports VEGF-VEGFR2 activity and may be useful for studying the pharmacodynamics of targeted angiogenesis inhibitors.
Magnetic Fields at Uranus (1986)

The magnetic field experiment on the Voyager 2 spacecraft revealed a strong planetary magnetic field of Uranus and an associated magnetosphere and fully developed bipolar masnetic tail. The detached bow shock wave in the solar wind supersonic flow was observed upstream at 23.7 Uranus radii (1 R(U) = 25,600 km) and the magnetopause boundary at 18.0 R(U), near the planet-sun line. A miaximum magnetic field of 413 nanotesla was observed at 4.19 R(U ), just before closest approach. Initial analyses reveal that the planetary magnetic field is well represented by that of a dipole offset from the center of the planet by 0.3 R(U). The angle between Uranus' angular momentum vector and the dipole moment vector has the surprisingly large value of 60 degrees. Thus, in an astrophysical context, the field of Uranus may be described as that of an oblique rotator. The dipole moment of 0.23 gauss R(3)(U), combined with the large spatial offset, leads to minimum and maximum magnetic fields on the surface of the planet of approximately 0.1 and 1.1 gauss, respectively. The rotation period of the magnetic field and hence that of the interior of the planet is estimated to be 17.29+/- 0.10 hours; the magnetotail rotates about the planet-sun line with the same period. Thelarge offset and tilt lead to auroral zones far from the planetary rotation axis poles. The rings and the moons are embedded deep within the magnetosphere, and, because of the large dipole tilt, they will have a profound and diurnally varying influence as absorbers of the trapped radiation belt particles.
In vivo recognition and clearance of red blood cells containing phosphatidylserine in their plasma membranes. (1985)

We have previously investigated the interaction of macrophages with red blood cells (RBC) displaying phosphatidylserine (PS) in their surface membranes after the transfer of the fluorescent lipid analog 1-acyl-2-[(N-4-nitrobenzo-2-oxa-1,3-diazole)aminocaproyl] phosphatidylserine to the RBC (Tanaka, Y., and Schroit, A. J. (1983) J. Biol. Chem. 258, 11335-11343). This derivative, which is rapidly transferred to the RBC at 37 degrees C, results in the efficient binding and phagocytosis of the RBC by autologous macrophages. In the present study, we show that 51Cr-labeled RBC containing [(N-4-nitrobenzo-2-oxa-1,3-diazole)-aminododecanoyl]phosphatidylserine (NBD-PS) are rapidly cleared from the peripheral circulation of syngeneic mice and accumulate in the liver and spleen. Fluorescence microscopy of Kupffer cells and splenic macrophages isolated from the liver and spleens of these animals revealed phagocytosed fluorescent RBC, suggesting the clearance was probably due to endocytosis of the RBC. The accumulation of these RBC in the spleen was dramatic, with approximately 30% of the injected cells localizing in this organ within 60 min. In contrast, the intravenous injection of RBC containing similar amounts of NBD-phosphatidylcholine or NBD-phosphatidylglycerol did not result in clearance which differed significantly from control (untreated) RBC populations. The observed clearance of NBD-PS-containing RBC was much different than the clearance of opsonized RBC which preferentially localized in the liver. These findings show that PS in RBC can serve as a signal for triggering their in vivo recognition and concomitant elimination from the circulation and suggest that the exposure of endogenous PS in the outer leaflet of RBC which occurs in certain pathological conditions could trigger their removal from the circulation.
Isolation of Mycoplasma bovis from bulk milk. (1985)

The prevalence of mycoplasma in Vermont dairy farms was determined by two surveys conducted in March 1983 and January 1984. Bulk tank milk samples representing 74% and 62% of the herds respectively were cultured. Mycoplasma bovis was detected in 3 of the 2,346 bulk samples collected in the initial survey. The infection rate was 1.3 herds per thousand (95% confidence interval: 0.6-2.0 herds per thousand). No positive cultures were obtained in the second survey.
Immunomodulation by methimazole therapy in Graves' disease: rapid changes in activation stage of circulating regulatory T cell subsets, B cells and NK cells. (1988)

In patients with Graves' disease, initiation of thyrostatic therapy with methimazole causes a selective reduction of thyroid but not other autoantibody levels. The mechanism of this immunosuppressive effect is unknown. In the present study, methimazole (20 mg daily) induced very rapid changes in the surface antigen expression of several circulating lymphocyte subpopulations in six patients with Graves' disease. Within 1 to 3 days of therapy, the proportions of HLA-DR+ cells within the CD8+(Leu 2+) subset (activated 'suppressor/cytotoxic' T cells), CD11+(Leu 15+) cells out of CD8+ cells ('suppressor' T cells), and CD45+R (Leu 18+) cells out of CD4+(LEU 3+) cells ('suppressor/inducer' T cells) increased significantly from 4.7 +/- 3.9% to 9.5 +/- 6.0%, from 7.5 +/- 1.5% to 17 +/- 5.8% and from 49 +/- 17% to 73 +/- 19%, respectively. In parallel, the percentages of DR+ cells within the CD4+(Leu 3+) subset (activated 'helper' T cells), 4F2+ cells out of CD19+(Leu 12+) cells (activated B cells) and 4F2+ cells out of CD16+(Leu 11+) cells (activated 'natural killer'-like cells) declined significantly from 7.2 +/- 5.6% to 2.8 +/- 2.1%, from 7.2 +/- 1.5% to 4.0 +/- 2.8% and from 5.5 +/- 3.5% to 2.8 +/- 4.9% at 3 days, respectively. In contrast, no consistent phenotypic changes occurred in lymphocytes drawn from six healthy subjects during 7 days of methimazole medication. Direct in vitro effects of methimazole on lymphocyte markers were not observed when blood mononuclear cells from untreated patients were incubated with either the drug (10(-4) and 10(-6)M) or with autologous pre/post treatment serum for 1 to 4 days. Methimazole thus induces rapid alterations in the subclass and activation marker expression of circulating lymphocyte populations in Graves' disease. These alterations are compatible with a down-regulation of B cell activity. Indirect evidence suggests that the thyroid gland is the source of secondary signals for these changes to take place.
Influenza Human Monoclonal Antibody 1F1 Interacts with Three Major Antigenic Sites and Residues Mediating Human Receptor Specificity in H1N1 Viruses (2012)

Most monoclonal antibodies (mAbs) to the influenza A virus hemagglutinin (HA) head domain exhibit very limited breadth of inhibitory activity due to antigenic drift in field strains. However, mAb 1F1, isolated from a 1918 influenza pandemic survivor, inhibits select human H1 viruses (1918, 1943, 1947, and 1977 isolates). The crystal structure of 1F1 in complex with the 1918 HA shows that 1F1 contacts residues that are classically defined as belonging to three distinct antigenic sites, Sa, Sb and Ca(2). The 1F1 heavy chain also reaches into the receptor binding site (RBS) and interacts with residues that contact sialoglycan receptors and determine HA receptor specificity. The 1F1 epitope is remarkably similar to the previously described murine HC63 H3 epitope, despite significant sequence differences between H1 and H3 HAs. Both antibodies potently inhibit receptor binding, but only HC63 can block the pH-induced conformational changes in HA that drive membrane fusion. Contacts within the RBS suggested that 1F1 may be sensitive to changes that alter HA receptor binding activity. Affinity assays confirmed that sequence changes that switch the HA to avian receptor specificity affect binding of 1F1 and a mAb possessing a closely related heavy chain, 1I20. To characterize 1F1 cross-reactivity, additional escape mutant selection and site-directed mutagenesis were performed. Residues 190 and 227 in the 1F1 epitope were found to be critical for 1F1 reactivity towards 1918, 1943 and 1977 HAs, as well as for 1I20 reactivity towards the 1918 HA. Therefore, 1F1 heavy-chain interactions with conserved RBS residues likely contribute to its ability to inhibit divergent HAs.
Beta-cyclodextrins as vehicles in eye-drop formulations: an evaluation of their effects on rabbit corneal epithelium. (1990)

Beta-cyclodextrins are cyclic molecules with a hydrophilic outer side and a central hydrophobic cavity. Through the inclusion of drug molecules into their cavities, i.e. the formation of inclusion complexes, cyclodextrins are able to modify the physical and chemical properties of these molecules. When used in pharmaceutical formulations, they can improve the aqueous solubility, stability, dissolution rate, bioavailability and/or local tolerance of certain drugs. To make an initial evaluation of the potential use of beta-cyclodextrins as vehicles in ophthalmic eye-drop formulations, we studied the effect of a single and of multiple applications of hydroxypropyl-beta-cyclodextrin (HP-beta-CD) 12.5% and of dimethyl-beta-cyclodextrin (DM-beta-CD) 5 and 12.5% solutions on the corneal epithelium of albino and pigmented rabbits with slit lamp biomicroscopy (SLB) and scanning electron microscopy (SEM). We can conclude from this study that DM-beta-CD at concentrations of 5 and 12.5% is not a suitable vehicle for ophthalmic formulations since it is toxic to the corneal epithelium and that HP-beta-CD at a concentration of 12.5% is well tolerated by the rabbit eye and is not toxic to the corneal epithelium when evaluated by SLB and SEM.
Lateral Diffusion of Inositol 1,4,5-Trisphosphate Receptor Type 1 Is Regulated by Actin Filaments and 4.1N in Neuronal Dendrites (2004)

Inositol 1,4,5-trisphosphate receptor type1 (IP3R1) plays an important role in neuronal functions; however, the lateral diffusion of IP3R1 on the endoplasmic reticulum membrane and its regulation in the living neurons remain unknown. We expressed green fluorescent protein-tagged IP3R1 in cultured rat hippocampal neurons and observed the lateral diffusion by the fluorescence recovery after photobleaching technique. IP3R1 showed lateral diffusion with an effective diffusion constant of approximately 0.3 microm2/s. Depletion of actin filaments increased the diffusion constant of IP3R1, suggesting that the diffusion of IP3R1 is regulated negatively through actin filaments. We also found that protein 4.1N, which binds to IP3R1 and contains an actin-spectrin-binding region, was responsible for this actin regulation of the IP3R1 diffusion constant. Overexpression of dominant-negative 4.1N and blockade of 4.1N binding to IP3R1 increased the IP3R1 diffusion constant. The diffusion of IP3R type 3 (IP3R3), one of the isoforms of IP3Rs lacking the binding ability to 4.1N, was not dependent on actin filaments but became dependent on actin filaments after the addition of a 4.1N-binding sequence. These data suggest that 4.1N serves as a linker protein between IP3R1 and actin filaments. This actin filament-dependent regulation of IP3R1 diffusion may be important for the spatiotemporal regulation of intracellular Ca2+ signaling.
The reaction of 1-tetralones with thallium trinitrate supported on clay: ring contraction vs alpha-oxidation (2001)

The reaction of a series of 1-tetralones with thallium trinitrate supported on Montmorillonite K-10 clay led to products of ring contraction (methyl indan-1-carboxylates) and/or alpha-oxidation (2-methoxy-1-tetralones), in variable yields.
Tissue Engineered Neocartilage Using Plasma Derived Polymer Substrates and Chondrocytes (1998)

This study demonstrates that fibrin monomers can be polymerized into moldable gels and used for the encapsulation of isolated chondrocytes. This biologically derived scaffold will maintain three-dimensional spatial support, allowing new tissue development in a subcutaneous space. Chondrocytes isolated from the glenohumeral and humeroradioulnar joints of a calf were combined with cyroprecipitate and polymerized with bovine thrombin to create a fibrin glue gel with a final cell density of 12.5 x 10(6) cells/ml. The polymer-chondrocyte constructs were implanted subcutaneously in 12 nude mice and incubated for 6 and 12 weeks in vivo. Histologic and biochemical analysis including deoxyribonucleic acid (DNA) and glycosaminoglycan quantitation confirmed the presence of actively proliferating chondrocytes with production of a well-formed cartilaginous matrix in the transplanted samples. Control specimens from 12 implantation sites consisting of chondrocytes alone or fibrin glue substrates did not demonstrate any gross or histologic evidence of neocartilage formation. Moldable autogenous fibrin glue polymer systems have a potential to serve as alternatives to current proprietary polymer systems used for tissue engineering cartilage as well as autogenous grafts and alloplastic materials used for facial skeletal and soft-tissue augmentation.
Flavopiridol in Untreated or Relapsed Mantle-Cell Lymphoma: Results of a Phase II Study of the National Cancer Institute of Canada Clinical Trials Group (2003)

Flavopiridol given as a daily bolus for 3 consecutive days every 3 weeks has modest activity as a single agent for mantle-cell lymphoma. The number of stable and partial responses that was seen indicates that it is biologically active and may delay progression. Future studies in mantle-cell lymphoma should test this agent with other active agents and using different schedules.
Genetic manipulation of genomes with rare-cutting endonucleases (1996)

DNA double-strand breaks (DSBs) pose a threat to the genomic integrity of a cell. The failure to heal a break or the inappropriate repair of a break can result in the loss of genetic information and other potentially deleterious consequences, such as chromosomal translocations. Recent developments using rare-cutting endonucleases have allowed investigators to introduce one or a few DSBs into complex genomes. Such studies have begun to elucidate the complex mechanisms of nonhomologous and homologous repair used by mammalian cells to repair these lesions. A key finding is that gene targeting is stimulated two to three orders of magnitude by a DSB at the target locus. Thus, the use of rare-cutting endonucleases and the co-opting of cellular repair mechanisms might provide scientists with another tool for engineering changes into genomes.