gebhart/patrepeval huggingface dataset:
Pleiotrophin signals increased tyrosine phosphorylation of β-catenin through inactivation of the intrinsic catalytic activity of the receptor-type protein tyrosine phosphatase β/ζ (2000)

Pleiotrophin (PTN) is a platelet-derived growth factor-inducible, 18-kDa heparin-binding cytokine that signals diverse phenotypes in normal and deregulated cellular growth and differentiation. To seek the mechanisms of PTN signaling, we studied the interactions of PTN with the receptor protein tyrosine phosphatase (RPTP) beta/zeta in U373-MG cells. Our results suggest that PTN is a natural ligand for RPTP beta/zeta. PTN signals through "ligand-dependent receptor inactivation" of RPTP beta/zeta and disrupts its normal roles in the regulation of steady-state tyrosine phosphorylation of downstream signaling molecules. We have found that PTN binds to and functionally inactivates the catalytic activity of RPTP beta/zeta. We also have found that an active site-containing domain of RPTP beta/zeta both binds beta-catenin and functionally reduces its levels of tyrosine phosphorylation when added to lysates of pervanidate-treated cells. In contrast, an (inactivating) active-site mutant of RPTP beta/zeta also binds beta-catenin but fails to reduce tyrosine phosphorylation of beta-catenin. Finally, in parallel to its ability to inactivate endogenous RPTP beta/zeta, PTN sharply increases tyrosine phosphorylation of beta-catenin in PTN-treated cells. The results suggest that in unstimulated cells, RPTP beta/zeta is intrinsically active and functions as an important regulator in the reciprocal control of the steady-state tyrosine phosphorylation levels of beta-catenin by tyrosine kinases and phosphatases. The results also suggest that RPTP beta/zeta is a functional receptor for PTN; PTN signals through ligand-dependent receptor inactivation of RPTP beta/zeta to increase levels of tyrosine phosphorylation of beta-catenin to initiate downstream signaling. PTN is the first natural ligand identified for any of the RPTP family; its identification provides a unique tool to pursue the novel signaling pathway activated by PTN and the relationship of PTN signaling with other pathways regulating beta-catenin.
Efficient delivery of dsRNA into zona‐enclosed mouse oocytes and preimplantation embryos by electroporation (2002)

Conditions for the electroporation of mouse oocytes and preimplantation embryos have been optimised by following the incorporation of rhodamine labeled dextran. This procedure includes a step to weaken but not remove the zona pellucida that helps achieve good survival. This approach has been applied to introduce double-stranded RNA for c-mos into oocytes and green fluorescent protein (GFP) into transgenic GFP-expressing embryos at the 1- and 4-cell stages. In both cases we were able to observe sequence-specific interference with the expression of the target gene--a failure of oocytes to arrest at metaphase II and a loss in the green fluorescence of embryos by the morula or blastocyst stages. These effects could be observed in multiple oocytes or embryos allowed to develop together following electroporation.
Identification of a Potent Agonist of the Orphan Nuclear Receptor Nurr1 (2006)

Benzimidazole-based Nurr1 agonists: Combinatorial chemistry and structure-based design were joined together to produce a lead-finding library of compounds focused on the nuclear receptor target family. A second-generation library directed against Nurr1, a specific orphan member of this family, was also prepared. This protocol allowed the discovery of a Nurr1 agonist with an EC50 value of 8 nM. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2452/2006/z600078_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Laser heating versus resistive heating in the field-desorption mass spectrometry of organic polymers (1988)

Laser heating of field-desorption emitters is evaluated against conventional resistive heating by comparing mass spectra of organic polymers (polypropylene glycol, polystyrene and polymethyl methacrylate). The temperature dependence of such spectra allows comparison at equivalent temperatures of the mass spectrometric sensitivities obtained with the two heating methods. No significant differences in sensitivity are observed. The power required for laser heating is 85% of that required using resistive heating to produce equivalent field desorption conditions.
Peroxiredoxin Evolution and the Regulation of Hydrogen Peroxide Signaling (2003)

Eukaryotic 2-Cys peroxiredoxins (2-Cys Prxs) not only act as antioxidants, but also appear to regulate hydrogen peroxide-mediated signal transduction. We show that bacterial 2-Cys Prxs are much less sensitive to oxidative inactivation than are eukaryotic 2-Cys Prxs. By identifying two sequence motifs unique to the sensitive 2-Cys Prxs and comparing the crystal structure of a bacterial 2-Cys Prx at 2.2 angstrom resolution with other Prx structures, we define the structural origins of sensitivity. We suggest this adaptation allows 2-Cys Prxs to act as floodgates, keeping resting levels of hydrogen peroxide low, while permitting higher levels during signal transduction.
Human enterocyte (Caco-2) migration is modulated in vitro by extracellular matrix composition and epidermal growth factor. (1992)

The modulation of enterocyte sheet migration was studied using Caco-2 cells, a well-differentiated human colonic cell line. Although Caco-2 cells attached and spread equivalently over collagen types I, III, IV, and V and laminin, migration over laminin was significantly slower than migration over the collagen types. Fibronectin was a poor substrate for attachment, spreading, and migration. Epidermal growth factor (EGF) stimulated migration over laminin but did not alter Caco-2 migration over collagen or fibronectin. This effect was independent of cell proliferation, which was stimulated equivalently on both laminin and collagen I. Expression and organization of cell surface receptors for matrix (integrins) were studied using antibodies specific for beta and alpha integrin subunits. Integrin surface expression was assessed by immunoprecipitation of surface 125iodinated control and EGF-treated cells. Beta 1 surface pools did not change substantially in any condition studied. Alpha 1 subunit pools were decreased after EGF treatment on collagen I but alpha 1 pools increased after EGF treatment on laminin. Surface pools of alpha 2 subunits were increased following EGF treatment whether cells were cultured on laminin or collagen I. However, traditional immunofluorescent and laser confocal imaging demonstrated substantial differences in the character of alpha 2 subunit organization between collagen and laminin in the migrating cell front. Furthermore, a functional antibody to the alpha 2 subunit inhibited EGF stimulation of migration over laminin without substantial effects on basal migration over laminin or collagen I. Thus, EGF appears to exert a matrix-specific effect on enterocyte migration by modulation of integrin expression and organization.
ChemInform Abstract: Synthesis and Pharmacological Properties of Some 4‐(2′‐Benzo[b]furanyl)coumarins. (1986)

Abstract Title compounds of type (II I) can be synthesized directly by reaction of the coumarins (I) with the salicylaldehydes (II) under re?ux.
Paroxysmal cold haemoglobinuria caused by non‐Hodgkin's lymphoma (1999)

Paroxysmal cold haemoglobinuria is an autoimmune haemolytic anaemia characterized by a biphasic polyclonal IgG autoantibody, the Donath-Landsteiner (D-L) antibody. Although classically described in association with chronic syphilis, it is most commonly seen after acute viral infections in children. We describe a case of high-grade B-cell non-Hodgkin's lymphoma which presented with paroxysmal cold haemoglobinuria. The lymphoma responded promptly to combination chemotherapy whilst, at the same time, the haemolytic process rapidly resolved. Subsequent investigations showed that the D-L antibody originated from the lymphoma cells.
Gate current leakage and breakdown mechanism in unpassivated AlGaN∕GaN high electron mobility transistors by post-gate annealing (2005)

Gate leakage/breakdown mechanism in unpassivated AlGaN∕GaN high electron mobility transistors (HEMTs) is investigated by performing temperature-dependent pulsed current–voltage (I–V) and current transient measurements of AlGaN∕GaN HEMTs without and with annealing after Schottky gate formation. After post-gate annealing, the devices exhibited significantly smaller gate leakage current and higher breakdown voltage even without any gate dielectrics or passivation layer. The temperature-dependent current transient measurements show that the current dispersion in the unannealed HEMTs is attributed to traps with an emission time constant (tE) of ∼0.5μs at 295 K and an activation energy of ∼38meV. On the contrary, the 20-min annealed devices have traps with tE of 21.6μs at 295 K and an activation energy of ∼0.31eV. The results suggest that the post-gate annealing removes shallow traps, and creates or activates deeper traps. We propose that the breakdown and gate leakage current is mainly due to the emission current from shallow traps in unpassivated AlGaN∕GaN HEMTs. The breakdown voltage improvement after the post-gate annealing is due to the removal of shallow traps near the Schottky gate metal∕AlGaN interface.
Antibodies against GD2 ganglioside can eradicate syngeneic cancer micrometastases. (1998)

After 10 years of clinical trials in patients with advanced cancer, monoclonal antibodies (mAbs) against cell surface antigens have not lived up to their initial promise. One such cell surface antigen is the ganglioside GD2. GD2 is richly expressed at the cell surfaces of human neuroblastomas, sarcomas, and melanomas. We have described a murine lymphoma (EL4) that is syngeneic in C57BL/6 mice and expresses GD2, a mAb against GD2 (mAb 3F8), and we have prepared a conjugate vaccine (GD2-keyhole limpet hemocyanin plus immunological adjuvant QS-21) that consistently induces antibodies against GD2. We demonstrate here, for the first time in a syngeneic murine model, that passively administered and vaccine-induced antiganglioside antibodies prevent outgrowth of micrometastases, and we use this model to establish some of the parameters of this protection. The level of protection was proportional to antibody titer. Treatment regimens resulting in the highest titer antibodies induced the most protection, and protection was demonstrated even when immunization was initiated after tumor challenge. Treatment with 3F8 1, 2, or 4 days after i.v. tumor challenge was highly protective, but waiting until 7 or 10 days after challenge resulted in minimal protection. The results were similar whether number of liver metastases or survival was used as the end point. These results suggest that unmodified mAbs or antibody-inducing vaccines against GD2 (and possibly other cancer cell surface antigens) should be used exclusively in the adjuvant setting, where circulating tumor cells and micrometastases are the primary targets.
Development of XUV projection lithography at 60--80 nm (1992)

The rationale, design, component properties, and properties, and potential capablilities of extreme-ultraviolet (XUV) projection lithography systems using 60--80 nm illumination and single-surface reflectors are described. These systems are evaluated for potential application to high-volume production of future generations of gigabit chips.
Efficient Automated Synthesis of Molecular Beacons (1999)

Abstract Automated synthesis of molecular beacons using 4-(4-dimethylamino phenylazo) benzoic acid (dabcyl) support and phosphoramidite is described.
Williams syndrome: From genotype through to the cognitive phenotype (2000)

Williams syndrome, due to a contiguous gene deletion at 7q11.23, is associated with a distinctive facial appearance, cardiac abnormalities, infantile hypercalcemia, and growth and developmental retardation. The deletion is approximately 1.5Mb and includes approximately 17 genes. Large repeats containing genes and pseudogenes flank the deletion breakpoints, and the mutation mechanism commonly appears to be unequal meiotic recombination. Elastin hemizygosity is associated with supravalvular aortic stenosis and other vascular stenoses. LIM Kinase 1 hemizygosity may contribute to the characteristic cognitive profile. The relationship of the other deleted genes to phenotypic features is not known. People with Williams syndrome tend to be over friendly-though anxious-and lack social judgement skills. They exhibit an uneven cognitive-linguistic profile together with mild to severe mental retardation. Analysis of the cognitive phenotype based on analyses of the mental processes underlying overt behavior demonstrates major differences between normal and WS subjects although for some areas, such as face processing, WS subjects can achieve near normal scores. Cognitive analysis of patients with small deletions in 7q11.23 which include elastin and LIM Kinase 1 have revealed varying results and it is premature to draw genotype-phenotype correlations.
Observation of Vibrational Excitation and Deexcitation for NO(v=2)Scattering from Au(111): Evidence for Electron-Hole-Pair Mediated Energy Transfer (2000)

Measurements of vibrational excitation and deexcitation of NO (v = 2) scattering from a Au(111) surface show that the probability of both processes increases strongly with the kinetic energy of the incident NO. These results are qualitatively consistent with a vibrational energy transfer mechanism involving electron-hole pairs but not with competing adiabatic models. The form of the energy dependence, and other features of the measurements, are not in accord with existing calculations.
P352: Ultrasound assessment of umbilical blood flow before and after laser therapy: An approach to the etiology of twin-twin transfusion syndrome (2003)

To estimate the volume and direction of blood exchange between the donor twin and recipient twin by ultrasound assessment of blood flow in the umbilical vein (UV) before and after selective laser photocoagulation of communicating vessels (SLPCV) for twin-twin transfusion syndrome (TTTS). Forty-seven TTTS patients underwent B-mode and pulsed Doppler examination of the UV before and 24-hours after SLPCV. Vein inner diameter (VD) was taken vertically with magnification of the image. The VD and mean time-average velocities (VTI) of the UV were estimated before and after surgery. Total umbilical venous flow (TUVF) was estimated as follows: TUVF (mL/min) = mean VTI (cm/s) × mean cross-sectional area (cm2) × 60. The surgeries were approved by the Institutional Review Board at St. Joseph's Hospital, and all patients gave informed written consent. TUVF was significantly higher in the recipient twin before SLPCV (100.3 mL/min vs. 36.5 mL/min in the donor twin, p < 0.0001). However, TUVF was no different between the fetuses after SLPCV (75.4 mL/min vs. 66.5 mL/min, recipient and donor, respectively, p = 0.17). The median post-op change in TUVF was + 29.5 mL/min for the donor twin and − 35.5 mL/min for the recipient twin, which were not statistically different (p =0.34). Our data suggests that TTTS may indeed be characterized by an excess flow of blood from the donor to the recipient twin, with a corresponding decrease after laser therapy. Accurate estimation of the actual blood volume exchange will require assessment of blood flow within each vascular anastomosis. Such an approach is currently under investigation by our group.
Precise intracavity phase interferometry in an optical parametric oscillator with two pulses per cavity round trip (2010)

Phase shifts of less than 10(-7) rad are measured through intracavity phase interferometry, a figure that corresponds to cavity length changes of the order of femtometers. The technique is demonstrated with a synchronously pumped optical parametric oscillator. By applying the technique to the measurement of the nonlinear index of refraction of lithium niobate, it is shown that higher accuracy and sensitivity than the traditional z-scan method can be achieved.
Substrate Specificity of Human O6-Methylguanine-DNA Methyltransferase for O6-Benzylguanine Derivatives in Oligodeoxynucleotides (1997)

To investigate the substrate specificity of human O6-methylguanine-DNA methyltransferase (MGMT) for O6-benzylguanine (6BG) derivatives incorporated in oligodeoxynucleotides, we prepared 25-mer lengths of sequences containing various 6BG derivatives and their related compounds and then measured the ability of these derivatives to inactivate MGMT in vitro. Oligodeoxynucleotides containing a 6BG, O6-(2-fluorobenzyl)guanine (2F-6BG), O6-(3-fluorobenzyl)guanine (3F-6BG), O6-(4-fluorobenzyl)guanine (4F-6BG), O6-benzylhypoxanthine (6BH), or O6-methylguanine (6MG) were all good substrates for MGMT, and no obvious differences were observed among them. Oligodeoxynucleotides containing N2-isobutyrylated 6BG and 6MG showed only a slightly reduced capacity for inactivating MGMT compared to N2-nonmodified forms of these derivatives. No obvious differences were observed in the corresponding double-stranded and single-stranded oligodeoxynucleotides. MGMT substrate specificity for the 6BG derivatives in the oligodeoxynucleotide was found to be quite different from that seen in our previous study [Mineura, K., et al. (1994) Int. J. Cancer 58, 706-712; (1995) Int. J. Cancer 63, 148-151. Kohda, K., et al. (1995) Biol. Pharm. Bull. 18, 424-430] and others [Moschel, R. C., et al. (1992) J. Med. Chem. 35, 4486-4491. Chae, M.Y., et al. (1994) J. Med. Chem. 37, 342-347] using the corresponding free bases. In brief, (i) 6BG, 3F-6BG, and 4F-6BG greatly inhibited human MGMT, whereas 2F-6BG, 6BH, and 6MG displayed much weaker activity; (ii) any modifications at the 2-amino group of the 6BG resulted in severe reductions in the ability to inactivate MGMT. These results obtained by the experiments using oligodeoxynucleotides and free bases suggest that human MGMT has low substrate specificity for 6BGs in oligodeoxynucleotides. Conformational changes in human MGMT which favor binding to oligodeoxynucleotides containing 6BG derivatives and the subsequent transfer of their benzyl groups may account for the difference in substrate specificity between the incorporated 6BG derivatives and their free base form.
Metabolic Functionalization of Recombinant Glycoproteins (2004)

Glycoproteins are essential for cellular communication and are the most rapidly growing class of therapeutic agents. Chemical modification of glycoproteins has been employed to improve their in vivo efficacy or to label them for detection. Methods for the controlled derivatization of glycoproteins are presently limited by the repertoire of natural amino acid side chain and carbohydrate functionalities. Here, we use metabolic oligosaccharide engineering to introduce a bioorthogonal functional group, the azide, into cellular and recombinant glycoproteins for subsequent chemical elaboration via Staudinger ligation. As most therapeutic glycoproteins are sialylated and require this saccharide for optimal pharmacokinetics, we targeted sialic acid as a host for azides using N-azidoacetylmannosamine (ManNAz) as a biosynthetic precursor. Metabolic conversion of ManNAz to N-azidoacetylsialic acid (SiaNAz) within membrane-bound and secreted glycoproteins was quantified in a variety of cell types. SiaNAz was found to comprise between 4% and 41% of total sialosides, depending on the system. Metabolic labeling of recombinant interferon-beta and GlyCAM-Ig was achieved, demonstrating the utility of the method for functionalizing N-linked and O-linked glycoproteins of therapeutic interest. More generally, the generation of recombinant glycoproteins containing chemical handles within their glycans provides a means for studying their behavior and for improving their in vivo efficacy.
A set of independent selectable markers for transfection of the human malaria parasite Plasmodium falciparum (1999)

Genomic information is rapidly accumulating for the human malaria pathogen, Plasmodium falciparum. Our ability to perform genetic manipulations to understand Plasmodium gene function is limited. Dihydrofolate reductase is the only selectable marker presently available for transfection of P. falciparum. Additional markers are needed for complementation and for expression of mutated forms of essential genes. We tested parasite sensitivity to different drugs for which selectable markers are available. Two of these drugs that were very effective as antiplasmodial inhibitors in culture, blasticidin and geneticin (G418), were selected for further study. The genes BSD, encoding blasticidin S deaminase of Aspergillus terreus, and NEO, encoding neomycin phosphotransferase II from transposon Tn 5, were expressed under the histidine-rich protein III (HRPIII) gene promoter and tested for their ability to confer resistance to blasticidin or G418, respectively. After transfection, blasticidin and G418-resistant parasites tested positive for plasmid replication and BSD or NEO expression. Cross-resistance assays indicate that these markers are independent. The plasmid copy number and the enzymatic activity depended directly on the concentration of the drug used for selection. These markers set the stage for new methods of functional analysis of the P. falciparum genome.
Synergy of fosfomycin with other antibiotics for Gram-positive and Gram-negative bacteria (2010)

The synergistic combination of fosfomycin with other antibiotics may be a useful alternative treatment option for Gram-negative and Gram-positive infections. Additional studies using more stringent definitions of synergy, and studies reporting on the clinical efficacy of fosfomycin combinations in the current era of high antimicrobial resistance are needed.
Updated overview of the putative role of the serotoninergic system in obsessive-compulsive disorder. (2005)

The pathophysiology of obsessive-compulsive disorder (OCD) remains unknown. However, increasing attention has been paid to the putative role of the serotoninergic system, the strongest evidence being based on the widely demonstrated efficacy of serotonin (5HT) reuptake inhibitor antidepressants in the treatment of OCD. The therapeutic effects are correlated with changes in peripheral parameters of 5HT function, which have been found to be altered in OCD, suggesting the possibility of reduced 5HT reuptake capacity. This could reflect a compensatory mechanism presumably due to decreased availability of extracellular 5HT, as evidenced by data derived from direct assessment of central 5HT neurotransmission. The development of new neurochemical probes that explore the sensitivity of various 5HT receptor subtypes has provided precious information. m-Chlorophenylpyperazine (m-CPP), an agonist to 5HT1A, 5HT1D, and 5HT2C receptors, and which also blocks 5HT3 receptors, exacerbates OC symptoms. In contrast, neither MK-212 (6-chloro-2-[1-piperazinyl]-pyrazine), a 5HT1A and 5HT2C receptor agonist, nor ipsapirone or buspirone, which acts as an agonist to 5HT1A receptors, have any effect on OC symptom severity. This suggests the potential implication of the 5HT1D receptor, as shown by the aggravation of OC manifestations in response to sumatriptan, a selective 5HT1D receptor agonist. The 5HT3 plays no specific role, given the lack of influence of the 5HT3 antagonist ondansetron, on OC symptom intensity. Further studies are required to elucidate the pharmacological molecular determinants of the putative 5HT1D receptor dysfunction.