gebhart/patrepeval huggingface dataset:
Experiments with high velocity positive ions.―(I) Further developments in the method of obtaining high velocity positive ions (1932)

Abstract In a previous communication we described the development of a method of obtaining positive ions of hydrogen with energies up to 300 kilovolts. A system of rectifiers was built which allowed steady potentials of this order to be obtained, and the methods necessary for the acceleration of positive ions from a hydrogen discharge tube were worked out. With this apparatus, investigations were made to determine whether any X-radiations or γ-radiations of appreciable intensity were produced by the impact of protons and molecular ions of hydrogen on matter. It was found, when all secondary effects were excluded, that if any such radiation is produced its intensity was comparable with the limits of error of the experiment, and was certainly not greater in intensity than one-millionth of the intensity of the continuous X-radiation which would have been produced by an equal electron source of the same energy. Since the intensity of any radiation would be expected to increase rapidly with the energy of the ions it became apparent that to obtain results of interest it would be necessary to extend the field of the work to higher voltages. The method used in the present experiments is an extension of that described in the previous paper. A source of high voltage has been developed, using thermionic rectifiers and condensers, which is capable of producing 800,000 volts steady potential. This potential is applied to an experimental tube down the axis of which protons from a hydrogen canal ray tube are accelerated. The protons can be transmitted through a mica window into an experimental chamber. Up to the present we have been able to produce and carry out experiments with protons having energies up to 710 kilovolts, and there seems no reason to doubt that the method will allow of this range being extended considerably.
Areas beneath the relative operating characteristics (ROC) and relative operating levels (ROL) curves: Statistical significance and interpretation (2002)

Abstract The areas beneath the relative (or receiver) operating characteristics (ROC) and relative operating levels (ROL) curves can be used as summary measures of forecast quality, but statistical significance tests for these areas are conducted infrequently in the atmospheric sciences. A development of signal‐detection theory, the ROC curve has been widely applied in the medical and psychology fields where significance tests and relationships to other common statistical methods have been established and described. This valuable literature appears to be largely unknown to the atmospheric sciences where applications of ROC and related techniques are becoming more common. This paper presents a survey of that literature with a focus on the interpretation of the ROC area in the field of forecast verification. We extend these foundations to demonstrate that similar principles can be applied to the interpretation and significance testing of the ROL area. It is shown that the ROC area is equivalent to the Mann–Whitney U ‐statistic testing the significance of forecast event probabilities for cases where events actually occurred with those where events did not occur. A similar derivation shows that the ROL area is equivalent to the Mann–Whitney U ‐statistic testing the magnitude of events with respect to whether or not an event has been forecast. Because the Mann–Whitney U ‐statistic follows a known probability distribution, under certain assumptions it can be used to define the statistical significance of ROC and ROL areas and for comparing the areas of competing forecasts. For large samples the significance of either measure can be accurately assessed using a normal‐distribution approximation. Copyright © 2002 Royal Meteorological Society
Anti-immunoglobulin in combination with cytochalasin stimulates proliferation of murine B lymphocytes. (1985)

The ability of cytochalasin to influence the stimulation of murine B lymphocytes through surface immunoglobulin was assessed during short term cultures. Modest doses of anti-immunoglobulin alone did not stimulate proliferation of mouse spleen cells at 2 days. Cytochalasin B alone also had no effect. However, anti-immunoglobulin in combination with cytochalasin B stimulated substantial proliferation as judged by [3H]thymidine incorporation. Cytochalasins A, E, and D, and dihydrocytochalasin B were all effective in promoting B cell proliferation. Spleen cells from xid-defective (CBA/N X DBA/2)F1 male mice failed to proliferate in response to anti-immunoglobulin plus cytochalasin, suggesting that this treatment affects the same subset of B cells as anti-immunoglobulin plus B cell growth factor. Moreover, proliferation that was stimulated by anti-immunoglobulin plus cytochalasin B was not affected by T cell depletion. Cytochalasin may circumvent the need for, or replace, a second signal for proliferation.
Lactam-Stabilized Helical Analogues of the Analgesic μ-Conotoxin KIIIA (2011)

μ-Conotoxin KIIIA (μ-KIIIA) blocks mammalian voltage-gated sodium channels (VGSCs) and is a potent analgesic following systemic administration in mice. Previous structure-activity studies of μ-KIIIA identified a helical pharmacophore for VGSC blockade. This suggested a route for designing truncated analogues of μ-KIIIA by incorporating the key residues into an α-helical scaffold. As (i, i+4) lactam bridges constitute a proven approach for stabilizing α-helices, we designed and synthesized six truncated analogues of μ-KIIIA containing single lactam bridges at various locations. The helicity of these lactam analogues was analyzed by NMR spectroscopy, and their activities were tested against mammalian VGSC subtypes Na(V)1.1 through 1.7. Two of the analogues, Ac-cyclo9/13[Asp9,Lys13]KIIIA7-14 and Ac-cyclo9/13[Lys9,Asp13]KIIIA7-14, displayed μM activity against VGSC subtypes Na(V)1.2 and Na(V)1.6; importantly, the subtype selectivity profile for these peptides matched that of μ-KIIIA. Our study highlights structure-activity relationships within these helical mimetics and provides a basis for the design of additional truncated peptides as potential analgesics.
Targeting CXCL12 from FAP-expressing carcinoma-associated fibroblasts synergizes with anti–PD-L1 immunotherapy in pancreatic cancer (2013)

An autochthonous model of pancreatic ductal adenocarcinoma (PDA) permitted the analysis of why immunotherapy is ineffective in this human disease. Despite finding that PDA-bearing mice had cancer cell-specific CD8(+) T cells, the mice, like human patients with PDA, did not respond to two immunological checkpoint antagonists that promote the function of T cells: anti-cytotoxic T-lymphocyte-associated protein 4 (α-CTLA-4) and α-programmed cell death 1 ligand 1 (α-PD-L1). Immune control of PDA growth was achieved, however, by depleting carcinoma-associated fibroblasts (CAFs) that express fibroblast activation protein (FAP). The depletion of the FAP(+) stromal cell also uncovered the antitumor effects of α-CTLA-4 and α-PD-L1, indicating that its immune suppressive activity accounts for the failure of these T-cell checkpoint antagonists. Three findings suggested that chemokine (C-X-C motif) ligand 12 (CXCL12) explained the overriding immunosuppression by the FAP(+) cell: T cells were absent from regions of the tumor containing cancer cells, cancer cells were coated with the chemokine, CXCL12, and the FAP(+) CAF was the principal source of CXCL12 in the tumor. Administering AMD3100, a CXCL12 receptor chemokine (C-X-C motif) receptor 4 inhibitor, induced rapid T-cell accumulation among cancer cells and acted synergistically with α-PD-L1 to greatly diminish cancer cells, which were identified by their loss of heterozygosity of Trp53 gene. The residual tumor was composed only of premalignant epithelial cells and inflammatory cells. Thus, a single protein, CXCL12, from a single stromal cell type, the FAP(+) CAF, may direct tumor immune evasion in a model of human PDA.
Treatment of Human B Cell Lymphoma Xenografts with a CD3 × CD19 Diabody and T Cells (2000)

The use of anti-CD3 x antitumor bispecific Abs is an attractive and highly specific approach in cancer therapy. Recombinant Ab technology now provides powerful tools to enhance the potency of such immunotherapeutic constructs. We designed a heterodimeric diabody specific for human CD19 on B cells and CD3epsilon chain of the TCR complex. After production in Escherichia coli and purification, we analyzed its affinity, stability, and pharmacokinetics, and tested its capacity to stimulate T cell proliferation and mediate in vitro lysis of CD19+ tumor cells. The effect of the diabody on tumor growth was investigated in an in vivo model using immunodeficient mice bearing a human B cell lymphoma. The CD3 x CD19 diabody specifically interacted with both CD3- and CD19-positive cells, was able to stimulate T cell proliferation in the presence of tumor cells, and induced the lysis of CD19+ cells in the presence of activated human PBL. The lytic potential of the diabody was enhanced in the presence of an anti-CD28 mAb. In vivo experiments indicated a higher stability and longer blood retention of diabodies compared with single chain Fv fragments. Treatment of immunodeficient mice bearing B lymphoma xenografts with the diabody and preactivated human PBL efficiently inhibited tumor growth. The survival time was further prolonged by including the anti-CD28 mAb. The CD3 x CD19 diabody is a powerful tool that should facilitate the immunotherapy of minimal residual disease in patients with B cell leukemias and malignant lymphomas.
Detection of early bronchial cancer by autofluorescence: results in patients with H&N cancer (2007)

Head and neck (H&N) cancer patients have a high incidence of second primary tumors in the tracheobronchial tree. Diagnostic autofluorescence endoscopy (DAFE) has shown promising results in the detection of early neoplastic and pre-neoplastic changes in the bronchi. We have investigated the medical impact of DAFE in a population of H&N cancer patients. The bronchoscopies were performed using a modified commercially available DAFE system, allowing both white light (WL) and autofluorescence (AF) bronchoscopy. Endoscopic imaging of the tissue AF was combined with an online image analysis procedure allowing to discriminate between true and false positive results. Twenty-one H&N cancer patients with a high risk of bronchial cancer underwent WL and AF bronchoscopy with this improved system. Forty-one biopsies were taken on macroscopically suspicious (WL or AF positive) bronchial sites. Histopathologic analysis confirmed pre- or early neoplastic changes in 11 of these biopsies taken from 8 patients. The sensitivity for the detection of these early lesions with the DAFE was 1.6 times larger than the sensitivity of WL bronchoscopy only. The positive predictive value (PPV) for AF was 79% (33% for WL alone). The PPV of both methods together was 100%. DAFE proved to be efficient for the detection of second primary lesions in H&N cancer patients. It can thus be used as a simple additional procedure to pre-operative or follow-up examination in this patient population.
Vaccination with Different M2e Epitope Densities Confers Partial Protection against H5N1 Influenza A Virus Challenge in Chickens (2011)

This study has provided evidence that the immune response to avian-type M2e-based subunit vaccines was greater in chickens than that in mice. In addition, higher M2e epitope density can yield better protection, but not in a linear fashion.
Evaluation of the TRUGENE HCV 5 ′ NC Genotyping Kit with the New GeneLibrarian Module 3.1.2 for Genotyping of Hepatitis C Virus from Clinical Specimens (2003)

The TRUGENE HCV 5'NC genotyping kit (GeneLibrarian modules 3.1.1 and 3.1.2) and VERSANT HCV genotyping assay were compared by using 96 hepatitis C virus (HCV) RNA-positive patient specimens, including HCV genotypes 1, 2, 3, 4, 5, 6, and 10. The TRUGENE HCV 5'NC genotyping kit (GeneLibrarian module 3.1.2) yielded the most accurate genotyping results.
Measurement of poliovirus RNA polymerase binding to poliovirion and nonviral RNAs using a filter-binding assay (1988)

The binding of the purified poliovirus RNA-dependent RNA polymerase to viral and nonviral RNAs was studied using a protein-RNA nitrocellulose filter binding assay. A cellular poly(A)-binding protein was found in viral polymerase preparations, but was easily separated from the polymerase by chromatography on poly(A) Sepharose. Optimal conditions for the binding of purified polymerase (fraction 5-PAS) to 32P-labeled poliovirion RNA were determined. The binding of purified polymerase to 32P-labeled ribohomopolymeric RNAs was examined, and the order of binding observed was poly(G) much much greater than poly(U) greater than poly(C) greater than poly(A). In competitive binding studies, the polymerase bound with equal efficiency to virion RNA and to a subgenomic transcript which contained the 3' end of the genome. The polymerase bound to 18S ribosomal RNA and to globin mRNA equally well, but with a five-fold lower affinity than to virus-specific RNAs. The results suggest that the polymerase exhibits sequence specificity in binding and that polymerase binding sites in poliovirus RNA may contain (G- and/or U)-rich sequences.
Surface orientation from a projected grid (1989)

Two simple methods are given for obtaining the surface shape using a projected grid. After the camera is calibrated to the 3-D workspace, the only input date needed for the computation of surface normals are grid intersect points in a single 2-D image. The first method performs nonlinear computations based on the distortion of the lengths of the grid edges and does not require a full calibration matrix. The second method requires that a full parallel projection model of the imaging is available, which enables it to compute 3-D normals using simple linear computations. The linear method performed better overall in the experiments, but both methods produced normals within 4-8 degrees of known 3-D directions. These methods appear to be superior to methods based on shape-from-shading because the results are comparable, yet the equipment setup is simpler and the processing is not very sensitive to object reflectance.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
The math behind the music (2007)

Preface Acknowledgments 1. Mathematics and music, a duet 2. Pitch: the ground of music 3. Tuning up 4. How to vary a theme mathematically 5. Bells and groups: music by chance 6. Pattern, pattern, pattern 7. Sight meets sound 8. How NOT to mix mathematics and music 9. Bibliography Contents of the CD Illustration credits Index.
The Glycan Moiety of Human Pancreatic Lithostathine. Structure Characterization and Possible Pathophysiological Implications (1995)

Lithostathine, also known as pancreatic stone protein, pancreatic thread protein or regenerating protein, is a glycoprotein which is normally found in the exocrine pancreas, whereas in other tissues it appears either only under pathological conditions, such as Alzheimer's disease (brain), cancer (colon) or during regeneration (endocrine pancreas). In the latter case, it has been shown recently that it acts as a growth factor which stimulates islet regeneration. Little is known about its glycan moiety, which conceivably might be involved in this tissue specificity and pathophysiological characteristics. Therefore we isolated the major oligosaccharide chains of human pancreatic lithostathine and determined their sequences by means of NMR analysis. We obtained eleven different glycoforms and we were able to determine the sequence of seven of them. They all were from the same site of glycosylation (Thr5) and displayed the same core 2 structure: GlcNAc(β1–6)[Gal(β1–3)]GalNAcα-. They ranged in size from 4 to 9 sugar residues. Elongation was found to proceed from a common tetrasaccharidic core: Gal(β1–4)GlcNAc(β1–6)[Gal(β1–3)]GalNAc-ol through N-acetyllactosamine units. The non-reducing ends of some oligosaccharides carry the antigenic determinant H, with presence of external Fuc linked only in (α1–2) to Gal. All the glycans, except one, carry a sialic acid in (α2–3) linkage to Gal, with one disialylated form which displays a supplementary (α2–6) linkage. These findings are consistent with the polymorphism of the protein, shown by means of SDS gel electrophoresis and isoelectric focusing, either in its native form or after enzymic processing. Moreover, sialylation seems to protect to some extent the Arg11-Ile12 bond from in situ hydrolysis, thus preventing the harmful precipitation of the C-terminal polypeptide in the pancreatic ducts.
Nucleic Acid Probes (1990)

Matters arisingneedle.Numerous well recognised texts state that this causes loss of the apirate into the body of the syringe, after which the aspirate will have to be repeated.'Metastasis to the track remains one of the rarer complications of needle biopsy or aspiration, but without further observation the effectiveness, or otherwise, ofmeasures to reduce the risk will remain uncertain.
Temporal and spatial control of the mother-cell regulatory gene spoIIID of Bacillus subtilis. (1989)

Gene expression during endospore formation in Bacillus subtilis is compartmentalized between the mother-cell and forespore chambers of the sporangium, which follow separate pathways of cellular differentiation. The earliest acting regulatory gene so far identified in the mother-cell line of gene expression is spoIIID, whose product is required for the transcription of the composite gene (sigK) encoding the mother-cell RNA polymerase sigma-factor sigma K and for the chromosomal rearrangement that gives rise to the composite gene. Here we report the nucleotide sequence of spoIIID and studies on the temporal, spatial, and genetic control of its expression during sporulation. We show that the deduced spoIIID gene product, a 93-residue-long polypeptide, is a previously identified transcription factor that is known to activate the promoter for the sigK gene in vitro. Expression of spoIIID is largely confined to the mother-cell chamber of the sporangium and is turned on at, or shortly before, the time (hour 3 of sporulation) that the mother-cell chromosome is rearranged and transcription of the sigK gene commences. This gene expression depends strongly on the sporulation sigma-factor sigma E and partially on the spoIIID gene product, itself. We conclude that the timing and compartmentalization of the rearrangement and transcription of the sigK gene and, hence, of subsequent gene activation in the mother cell, are, in part, direct consequences of the temporal and spatial control of spoIIID gene expression.
Collaborative study for the establishment of replacement batches for human coagulation factor IX concentrate reference standards. (2008)

The European Pharmacopoeia (Ph. Eur.) Biological Reference Preparation (BRP) batch 1, the World Health Organisation (WHO) 3rd International Standard, Human (IS, 96/854) and the FDA Standard for human blood coagulation Factor IX concentrate have been available since 1996, following their establishment by a common collaborative study. Due to dwindling stocks of all three standards, a new WHO-EDQM-FDA tri-partite collaborative study was launched to establish replacement batches. Thirty laboratories from fourteen countries took part in the collaborative study to assign potency values to candidate preparations. Three candidates, one of recombinant and two of human plasma-derived origins, were assayed against the 3rd IS for Blood Coagulation Factor IX, Concentrate, Human (96/854). The 3rd IS for Blood Coagulation Factors II, VII, IX and X, Plasma, Human (99/826) was also included to evaluate the relationship between the factor IX plasma and concentrate unitage. Thirty-two sets of clotting assay results and two sets of chromogenic assay data were analysed. There was a significant difference in potency estimates by these two methods for the recombinant candidate (sample B) and the plasma IS (sample P). Similar potency values were obtained for the plasma derived products (monoclonal antibody- and chromatography-purified factor IX, samples C and D) by clotting and chromogenic assays. For the clotting assays, intra-laboratory variability (GCV) was found to range from 0.5 - 21.7%, with the GCV for the majority of laboratories being less than 10%. Good inter-laboratory agreement, with the majority of the GCV being less than 10% (GCV range = 4.7 - 10.6 %) was also obtained. The mean potency values estimated by the clotting assay using plasma as pre-diluent (as directed by the Ph. Eur. general chapter method) did not differ from values obtained using buffer. Taking into account the preliminary stability data, the intra- and inter-laboratory variability, and the differences between the clotting and chromogenic assay results, sample C (07/182) was established as the Human coagulation factor IX concentrate BRP batch 2, with a potency value of 7.9 IU/ampoule assigned with clotting assay results. As an outcome of this tri-partite collaborative study, the same sample C (07/182) has also been adopted as the 4th International Standard for Blood Coagulation Factor IX, Concentrate, Human by the Expert Committee on Biological Standardisation (ECBS) of the World Health Organisation (WHO), and as the replacement batch for the reference standard for Human coagulation factor IX concentrate by the FDA.
Regulation of endothelial cell gap formation and barrier dysfunction: Role of myosin light chain phosphorylation (1995)

Endothelial cell (EC) contraction results in intercellular gap formation and loss of the selective vascular barrier to circulating macromolecules. We tested the hypothesis that phosphorylation of regulatory myosin light chains (MLC) by Ca2+/calmodulin-dependent myosin light chain kinase (MLCK) is critical to EC barrier dysfunction elicited by thrombin. Thrombin stimulated a rapid (< 15 sec) increase in [Ca2+]i which preceded maximal MLC phosphorylation (60 sec) with a 6 to 8-fold increase above constitutive levels of phosphorylated MLC. Dramatic cellular shape changes indicative of contraction and gap formation were observed at 5 min with maximal increases in albumin permeability occurring by 10 min. Neither the Ca2+ ionophore, A23187, nor phorbol myristate acetate (PMA), a direct activator of protein kinase C (PKC), alone or in combination, produced MLC phosphorylation. The combination was synergistic, however, in stimulating EC contraction/gap formation and barrier dysfunction (3 to 4-fold increase). Down-regulation or inhibition of PKC activity attenuated thrombin-induced MLC phosphorylation (approximately 40% inhibition) and both thrombin- and PMA-induced albumin clearance (approximately 50% inhibition). Agents which augmented [cAMP]i partially blocked thrombin-induced MLC phosphorylation (approximately 50%) and completely inhibited both thrombin- and PMA-induced EC permeability (100% inhibition). Furthermore, cAMP produced significant reduction in the basal levels of constitutive MLC phosphorylation. Finally, MLCK inhibition (with either ML-7 or KT 5926) or Ca2+/calmodulin antagonism (with either trifluoperazine or W-7) attenuated thrombin-induced MLC phosphorylation and barrier dysfunction. These results suggest a model wherein EC contractile events, gap formation and barrier dysfunction occur via MLCK-dependent and independent mechanisms and are significantly modulated by both PKC and cAMP-dependent protein kinase A activities.