gebhart/patrepeval huggingface dataset:
Experimental Characterization of Secular Frequency Scanning in Ion Trap Mass Spectrometers (2016)

Secular frequency scanning is implemented and characterized using both a benchtop linear ion trap and a miniature rectilinear ion trap mass spectrometer. Separation of tetraalkylammonium ions and those from a mass calibration mixture and from a pesticide mixture is demonstrated with peak widths approaching unit resolution for optimized conditions using the benchtop ion trap. The effects on the spectra of ion trap operating parameters, including waveform amplitude, scan direction, scan rate, and pressure are explored, and peaks at black holes corresponding to nonlinear (higher-order field) resonance points are investigated. Reverse frequency sweeps (increasing mass) on the Mini 12 are shown to result in significantly higher ion ejection efficiency and superior resolution than forward frequency sweeps that decrement mass. This result is accounted for by the asymmetry in ion energy absorption profiles as a function of AC frequency and the shift in ion secular frequency at higher amplitudes in the trap due to higher order fields. We also found that use of higher AC amplitudes in forward frequency sweeps biases ions toward ejection at points of higher order parametric resonance, despite using only dipolar excitation. Higher AC amplitudes also increase peak width and decrease sensitivity in both forward and reverse frequency sweeps. Higher sensitivity and resolution were obtained at higher trap pressures in the secular frequency scan, in contrast to conventional resonance ejection scans, which showed the opposite trend in resolution on the Mini 12. Mass range is shown to be naturally extended in secular frequency scanning when ejecting ions by sweeping the AC waveform through low frequencies, a method which is similar, but arguably superior, to the more usual method of mass range extension using low q resonance ejection. Graphical Abstract ᅟ.
Crystal Structure of Alkaline Phosphatase from Human Placenta at 1.8 Å Resolution (2001)

Human placental alkaline phosphatase (PLAP) is one of three tissue-specific human APs extensively studied because of its ectopic expression in tumors. The crystal structure, determined at 1.8-A resolution, reveals that during evolution, only the overall features of the enzyme have been conserved with respect to Escherichia coli. The surface is deeply mutated with 8% residues in common, and in the active site, only residues strictly necessary to perform the catalysis have been preserved. Additional structural elements aid an understanding of the allosteric property that is specific for the mammalian enzyme (Hoylaerts, M. F., Manes, T., and Millán, J. L. (1997) J. Biol. Chem. 272, 22781-22787). Allostery is probably favored by the quality of the dimer interface, by a long N-terminal alpha-helix from one monomer that embraces the other one, and similarly by the exchange of a residue from one monomer in the active site of the other. In the neighborhood of the catalytic serine, the orientation of Glu-429, a residue unique to PLAP, and the presence of a hydrophobic pocket close to the phosphate product, account for the specific uncompetitive inhibition of PLAP by l-amino acids, consistent with the acquisition of substrate specificity. The location of the active site at the bottom of a large valley flanked by an interfacial crown-shaped domain and a domain containing an extra metal ion on the other side suggest that the substrate of PLAP could be a specific phosphorylated protein.
An Empirical Analysis of Retailer Participation Decisions in a Downtown Parking Coupon Program (1998)

Parking coupon programs help downtown shopping areas attract consumers away from suburban shopping centers. Here we conduct an empirical analysis of retailer participation in such a program. Consistent with expectations, participation was higher for stores in shopping centers than for street‐front retailers, for stores receiving subsidies for coupon purchase, and for stores selling comparison‐shopping goods than for stores selling goods bought on one‐stop, single‐purpose or multipurpose‐shopping trips. Participation also varied with numbers of competitors, chain membership, and store vintage. Apparently, participation is a local public good for downtown retailers and stores are inclined to free ride.
Improved nonalcoholic steatohepatitis after 48 weeks of treatment with the PPAR-γ ligand rosiglitazone (2003)

Insulin resistance (IR) commonly is associated with nonalcoholic steatohepatitis (NASH). To establish whether IR causes NASH, this study was undertaken to determine if improving IR would improve the histologic features that define NASH. Thirty adults with prior biopsy evidence of NASH were enrolled to receive rosiglitazone, 4 mg twice daily for 48 weeks. All patients were overweight (body mass index [BMI] > 25 kg/m(2)) and 23% were severely obese (BMI > 35 kg/m(2)); 50% had impaired glucose tolerance or diabetes. Liver biopsy specimens were obtained before beginning treatment and at treatment completion. Twenty-six patients had posttreatment biopsies; of these, 22 had initial protocol liver biopsies that met published criteria for NASH on subsequent blinded evaluation. Within this initial NASH group, the mean global necroinflammatory score significantly improved with treatment and biopsies of 10 patients (45%) no longer met published criteria for NASH after treatment. Significant improvement in hepatocellular ballooning and zone 3 perisinusoidal fibrosis also occurred. Five patients withdrew early; the 25 patients completing 48 weeks of treatment had significantly improved insulin sensitivity and mean serum alanine aminotransferase (ALT) levels (104 initially, 42 U/L at the end of treatment). Adverse effects led to withdrawal of 3 patients (10%). Weight gain occurred in 67% of patients and the median weight increase was 7.3%. Within 6 months of completing treatment, liver enzyme levels had increased to near pretreatment levels. In conclusion, improving insulin sensitivity with rosiglitazone resulted in improved histologic markers of NASH, an observation suggesting that insulin resistance contributes to its development and that improving insulin sensitivity may be important in treating this liver disease.
Nucleotides part XXXII. Synthesis of a dithymidine dinucleotide containing a 3′: 5′-internucleotidic linkage (1955)

A. M. Michelson and A. R. Todd, J. Chem. Soc., 1955, 2632 DOI: 10.1039/JR9550002632
C4orf7 contributes to ovarian cancer metastasis by promoting cancer cell migration and invasion (2010)

Gene C4orf7, renamed FDC-SP (follicular dendritic cell secreted protein, FDC-SP) was first isolated from human tonsils. Up to the present, the function of this gene was still poorly understood. In this study, we report the expression of gene C4orf7 in a panel of tumor types. The percentages of C4orf7 positive expression in the tumor patients with metastases were notably higher than those in the cancer without metastases. On the contrary, the expression was hardly noted in normal tissues and corresponding benign lesions. In vitro, the up-regulation of C4orf7 in ovarian cancer cell lines was associated with enhanced motility and invasiveness. Furthermore, the overexpression of C4orf7 resulted in Akt ser473 phosphorylation and decreased E-cadherin expression. The role of C4orf7 in ovarian cancer cell morphology, motility and invasion was demonstrated.
The Association Of The Induction Of Vascular Cell Adhesion Molecule-1 With CytoMEGALOVIRUS ANTIGENEMIA IN HUMAN HEART ALLOGRAFTS (1993)

Previous studies have suggested that during acute heart allograft rejection the expression of vascular adhesion molecules is induced. This study was designated to investigate the expression of three adhesion molecules ICAM-1 (CD 54), VCAM-1, and ELAM-1, and the counter-ligands LFA-1 (CD 18), Mac-1 (CD 11b/CD 18), and VLA-4 (CD 49d) in frozen sections of endomyocardial biopsies (EMB) of heart allografts in relation to onset of CMV infection recorded as CMV antigenemia. The expression of MHC class II antigens and interleukin-2-receptor was also analyzed. A total of 105 EMBs and 840 immunoperoxidase stainings obtained from 21 heart transplant recipients were analyzed. EMBs from 9 patients with CMV infections, 5 patients with rejections, and 7 patients with a noncomplicated postoperative course were included. An induction of VCAM-1 occurred in relation to onset of CMV antigenemia. The expression of VCAM-1 remained elevated for several weeks declining slowly to control levels. Associated with CMV infection, capillary expression of VCAM-1 (P < 0.001) and ELAM-1 (P < 0.03) was significantly induced when compared with control biopsies. ICAM-1 expression was always seen in capillaries--and also in controls. A striking difference in the expression of VCAM-1 during rejection and CMV infection was observed: in most rejecting biopsies only a few capillaries stained faintly for VCAM-1, whereas during CMV infection multifocal intense staining was found (P < 0.0001). Induction of ELAM-1 was associated with acute rejections. In general, the expression of ligand counterparts was at a higher level during rejection compared with CMV infection. However, a short-term induction of VLA-4 occurred after the onset of CMV antigenemia (N.S.). Thus, the VCAM-1/VLA-4 ligand pair may play an important role in adhesion of lymphocytes and monocytes to capillary endothelium during active CMV infection and may also contribute to the pathogenesis of increased vasculopathic changes reported in CMV-infected heart transplant recipients.
T cell determinants from autoantibodies to DNA can upregulate autoimmunity in murine systemic lupus erythematosus. (1995)

(NZB x NZW) F1 (BWF1) mice develop spontaneous T cell autoimmunity to VH region determinants of syngeneic anti-DNA before the onset of clinical disease. In this study, we characterized the immunogenicity, MHC binding, and lymphokine secretion patterns induced by T cell determinants from the VH region of one such anti-DNA mAb (A6.1) and examined their role in the regulation of autoimmunity. Determinants were identified by proliferation of syngeneic splenic T cells from young, unprimed BWF1 mice in response to overlapping 12-mer peptides representing the entire VH region sequence. Immunization of young BWF1 mice with any of three determinants (A6H 34-45 [p34], A6H 58-69 [p58], and A6H 84-95 [p84]) elicited proliferative responses upon in vitro recall. Upon immunization with the whole A6.1 molecule, however, proliferative responses could be recalled only to the p58 peptide, defining this as immunodominant. The other two peptides (p34 and p84) elicited minimal or no proliferation and could be termed cryptic. Proliferative responses elicited by the cryptic determinants were restricted by a single class II (I-Ed for p34 and I-Au for p84), whereas the immunodominant p58 determinant was restricted by both I-Ed and I-Eu. The cryptic p34 and p84 bound strongly to I-Ed and I-Au, respectively, whereas the immunodominant p58 peptide bound poorly to I-Ed. A6H p84 elicited T cells that secreted lymphokines in a pattern consistent with a Th1-like phenotype, whereas p58 induced a Th2-like cytokine pattern. Immunization with p34 or p84, or adoptive transfer of a p84-reactive T cell line to young BWF1 mice significantly increased IgG anti-DNA levels, accelerated nephritis, and decreased survival. In conclusion, in BWF1 mice, autoreactive T cells recognizing both cryptic and dominant self-determinants on anti-DNA autoantibodies escape deletion or anergy induction. Furthermore, since these cells are spontaneously activated before the onset of clinical disease, they may be involved in the development of the autoimmune process.
Thermal stability of sodium hyaluronate in aqueous solution (1994)

Since its identification 60 years ago as a ubiquitous component of the body of mammals, hyaluronic acid has been widely studied, primarily in the fields of medicine and biology. On the other hand, our research has dealt with hyaluronic acid as a chemical intermediate in the synthesis of novel lubricious coatings, and in this connection data were needed on stability of aqueous solutions of the polymer over a range of temperatures from 25-100 degrees C. The investigation reported here provides that information, obtained by exposing samples in sealed ampules in baths at controlled temperatures and determining the resulting change in viscosity of the solutions. Data of this kind have not previously been reported on sodium hyaluronate freed from the proteins and other organics normally associated with the polymer in its natural environment.
Biosynthesis of endotoxins. Purification and catalytic properties of 3-deoxy-D-manno-octulosonic acid transferase from Escherichia coli. (1992)

The enzyme 3-deoxy-D-manno-octulosonic acid (Kdo) transferase is encoded by the kdtA gene of Escherichia coli and plays a key role in lipopolysaccharide biosynthesis. It transfers Kdo from CMP-Kdo to lipid A or its tetraacyldisaccharide-1,4'-bisphosphate precursor, lipid IVA. Using a strain that overproduces the transferase approximately 500-fold, we have purified the enzyme to near homogeneity. The subunit molecular mass is approximately 43 kDa. Activity is stimulated by Triton X-100, is maximal at pH 7, but does not require Mg2+. The apparent Km values for lipid IVA and CMP-Kdo are 52 and 88 microM, respectively. Vmax is 15-18 mumol/min/mg when both substrates are added near saturation at pH 8. The purified enzyme transfers 2 Kdo residues to lipid A precursors or analogs bearing four to six fatty acyl chains and a 4'-monosphosphate moiety. Activity is inhibited by polymixin B and Re endotoxin. At low Kdo concentrations small amounts of the intermediate, (Kdo)1-IVA, accumulate. When this substance is isolated and incubated with purified enzyme in the presence of CMP-Kdo, it is converted to (Kdo)2-IVA. Formation of (Kdo)1-IVA is also observed when purified enzyme is incubated with (Kdo)2-IVA and 5 mM CMP, demonstrating that Kdo transfer is reversible. In summary, Kdo transferase consists of a single bifunctional polypeptide that incorporates the 2 innermost Kdo residues common to all lipopolysaccharide molecules in E. coli.
Materials for enhancing cell adhesion by immobilization of cell‐adhesive peptide (1991)

Materials to enhance cell adhesion were synthesized by surface integration of peptide, Arg-Gly-Asp-Ser(RGDS), which is an active-site sequence of cell-adhesive proteins. Polystyrene film was glow-discharged and graft-copolymerized with acrylic acid. Then the peptide was immobilized to the poly(acrylic acid) grafts by using water-soluble carbodiimide. The cell-adhesive activity of the RGDS-immobilized film increased with increasing amount of immobilized peptide, and approached the activity of fibronectin(FN)-immobilized film. The RGDS-immobilized film was more stable against heat treatment and pH variation than the FN-immobilized film. In addition, the RGDS-immobilized film enhanced cell growth more strongly than the FN-immobilized film.
[Antiradical properties of Ginkgo biloba extract]. (1986)

The anti-radical properties of Ginkgo biloba extract have been determined on several in vitro models. The products is as effective as uric acid, an anti-radical agent known to entrap the hydroxyl and diphenylpicrylhydrazyl radicals. In addition, it inactivates the formation of radicals, such as adriamycyl, which escape uric acid activity. It also inhibits membrane lipid peroxidation and owes to its anti-radical activity exerts a stimulant effect on the biosynthesis of prostanoids.
J.J. Bonica lecture—2000: Physiology, pathophysiology, and pharmacology of visceral pain (2000)

All pelvic nerve fibers innervating the descending colon can be sensitized and contribute to visceral pain; their responses are modulated by kappa-opioid receptor agonists acting in the periphery.
Elimination of cycling CD4+ suppressor T cells with an anti-mitotic drug releases non-cycling CD8+ T cells to cause regression of an advanced lymphoma. (1990)

This paper describes a model of successful immunotherapy of advanced lymphoma based on the selective elimination of cycling tumour-induced suppressor T cells. It shows that a single injection of the anti-mitotic drug, vinblasting (Vb), results in complete regression of a large L5178Y lymphoma and its metastases, but not if it is growing in an immunocompetent host. Vb-induced, immunologically mediated tumour regression was dependent on the anti-tumour function of CD8+ T cells, because regression was prevented by depleting the host of this subset of T cells 24 hr after Vb was given. Regression was also prevented by infusing the host with Vb-sensitive, CD4+ T cells from a tumour-bearing donor. These and other results are in keeping with the interpretation that Vb-induced regression of the L5178Y lymphoma depends on the ability of the drug to eliminate CD4+ suppressor T cells that are replicating, and to spare non-replicating CD8+ effector cells. It is suggested that at an advanced stage of growth of the L5178Y lymphoma the host possesses an acquired population of antigen-primed CD8+ effector T cells that are unable to become activated in response to abundant tumour antigen because of the dominant influence of CD4+ suppressor cells. Activation of these CD8+ T cells was indicated by the finding that they were rapidly converted from being cyclophosphamide (Cy) resistant to being highly Cy sensitive within 48 hr of giving Vb.
Cyclodextrin-centred star polymers synthesized via a combination of thiol-ene click and ring opening polymerization (2012)

The synthesis of cyclodextrin-centred star polymers via thiol-ene addition of per-6-thio-β-cyclodextrin (CD-(SH)(7)) with vinyl terminated polymers is described. The obtained thiol-ene product was employed as an initiator for ring opening polymerization (ROP) of ε-caprolactone (ε-CL).
Energy balance in Alzheimer's disease. (2002)

Alzheimer s disease is the most frequent cause of dementia in elderly people and it is one of the leading causes of death among older individuals. Weight loss is a frequent clinical finding in Alzheimer s disease patients, and it is actually listed as a symptom consistent with the diagnosis of Alzheimer s disease, but its significance has not been clearly understood until now. This review examines the role of the components of energy balance in determining weight loss in AD patients, on the basis of data collected from the literature. We also considered the possible causes of anorexia in AD patients. In the last years many researchers investigated the possible role of abnormally high energy expenditure, or low energy intakes, or both, to explain weight loss in these patients. Studies on energy intake, energy expenditure and body composition in AD patients have been reviewed. The results of published studies do not seem to support the hypothesis of an hypermetabolic state or inadequate energy intake in AD patients, but further studies, with greater samples are necessary in the future to investigate weight loss in AD patients. A better understanding of this finding could be important to obtain the maximal lifespan of demented patients.
HBV Infection in Pediatric Liver Transplantation (1993)

When hepatitis B virus (HBV) infection precedes orthotopic liver transplantation (OLT), an important issue is to avoid post-OLT HBV infection of the transplanted liver. When HBV infection is found after OLT, the main objective is to prevent the complication of cirrhosis. A study of HBV infection in 162 liver-transplanted children followed at Hôpital de Bicêtre is presented here. One hundred forty-one of these children were completely vaccinated against HBV; 89% of them still disposed of protective titers of serum antibodies to hepatitis B surface antigen (anti-HBs) (> 10 IU/L) 6-60 months after OLT. Four children had a HBV-associated liver disease that required OLT. In these children a passive immunoprophylaxis maintaining serum anti-HBs levels > 100 IU/L allowed three of them to remain free of serum hepatitis B surface antigen (HBsAg) and HBV-DNA during follow-up at 10, 20, and 36 months. Four other children have been found to be HBsAg+ after OLT, but it was not clear whether the source of HBV was a reactivation or a de novo infection. Low doses of cyclosporin and prednisone were administered, in order to avoid the complications of HBV infection. Liver needle biopsies in three of these patients 37, 42, and 46 months after OLT showed a moderate chronic active hepatitis and mild fibrosis. Immunostaining for HBs and hepatitis B core (HBc) antigens indicated active viral replication.(ABSTRACT TRUNCATED AT 250 WORDS)
Practical fast searching in strings (1980)

Abstract The problem of searching through text to find a specified substring is considered in a practical setting. It is discovered that a method developed by Boyer and Moore can outperform even special‐purpose search instructions that may be built into the computer hardware. For very short substrings however, these special purpose instructions are fastest—provided that they are used in an optimal way.
Expression of Scatter Factor in Human Bladder Carcinoma (1995)

Quantitation of SF in the urine and tumor deserves further study as a possible marker of urothelial malignancy.
Axial-Selective Prins Cyclizations by Solvolysis of α-Bromo Ethers (2004)

Prins cyclizations are intramolecular electrophilic additions of oxocarbenium ions. They lead to tetrahydropyrans with a heteroatom at the 4-position, and usually show moderate-to-high selectivity for equatorial substitution. We have found that Prins cyclizations carried out under specific conditions produce tetrahydropyrans with almost exclusive formation of the axial 4-substituent. TMSBr, AcBr, and TMSI all lead to axial-selective Prins cyclizations with alpha-acetoxy ether substrates in the presence lutidine. The mechanism appears to involve solvolysis of the intermediate alpha-bromo ether rather than specific or Lewis acid-catalyzed rearrangement. The scope of the reaction, the high yields, and the stereoselectivity make this a valuable new method for tetrahydropyran formation.
Mechanism of Lymphocyte-Mediated Cytotoxicity (1985)

Exhausted CD8 T (Tex) cells are a distinct cell lineage that arise during chronic infections and cancers in animal models and humans. Tex cells are characterized by progressive loss of effector functions, high and sustained inhibitory receptor expression, ...Read More
Design and Synthesis of Non-Peptide, Selective Orexin Receptor 2 Agonists (2015)

Orexins are a family of neuropeptides that regulate sleep/wakefulness, acting on two G-protein-coupled receptors, orexin receptors 1 (OX1R) and 2 (OX2R). Genetic and pharmacologic evidence suggests that orexin receptor agonists, especially OX2R agonist, will be useful for mechanistic therapy of the sleep disorder narcolepsy/cataplexy. We herein report the discovery of a potent (EC50 on OX2R is 0.023 μM) and OX2R-selective (OX1R/OX2R EC50 ratio is 70) agonist, 4'-methoxy-N,N-dimethyl-3'-[N-(3-{[2-(3-methylbenzamido)ethyl]amino}phenyl)sulfamoyl]-(1,1'-biphenyl)-3-carboxamide 26.