gebhart/patrepeval huggingface dataset:
Natural Killer Cell–Mediated Eradication of Neuroblastoma Metastases to Bone Marrow by Targeted Interleukin-2 Therapy (1998)

Targeted interleukin-2 (IL-2) therapy with a genetically engineered antidisialoganglioside GD2 antibody-IL-2 fusion protein induced a cell-mediated antitumor response that effectively eradicated established bone marrow and liver metastases in a syngeneic model of neuroblastoma. The mechanism involved is exclusively natural killer (NK) cell-dependent, because NK-cell deficiency abrogated the antitumor effect. In contrast, the fusion protein remained completely effective in the T-cell-deficient mice or immunocompetent mice depleted of CD8+ T cells in vivo. A strong stimulation of NK-cell activity was also shown in vitro. Immunohistology of the leukocytic infiltrate of livers from treated mice revealed a strong staining for NK cells but not for CD8+ T cells. The therapeutic effect of the fusion protein was increased when combined with NK-cell-stimulating agents, such as poly I:C or recombinant mouse interferon-gamma. In conclusion, these data show that targeted delivery of cytokines to the tumor microenvironment offers a new strategy to elicit an effective cellular immune response mediated by NK cells against metastatic neuroblastoma. This therapeutic effect may have general clinical implications for the treatment of patients with minimal residual disease who suffer from T-cell suppression after high-dose chemotherapy but are not deficient in NK cells.
Focusing in transmit–receive mode through inhomogeneous media: The time reversal matched filter approach (1995)

For a few years, adaptive time delay focusing techniques have been extensively studied in order to focus through inhomogeneous media. However, these techniques can only correct the effects of a thin aberrator located near the array. Time reversal of ultrasonic fields allows another approach to focus in the transmit mode through inhomogeneous media. Compared to the adaptive time delay focusing technique, time reversal requires the transmission of different waveforms from each individual element of an array. Focusing via time reversal is shown to be optimal in comparison with time delay focusing since it realizes the spatio-temporally matched filter to the inhomogeneous propagation transfer function between the array and the focal point. In previous papers [Fink et al., Proc. IEEE Ultrasonics Symposium, Montreal (1989)], focusing by time reversal has been described in the transmit mode only. A complete focusing in inhomogeneous medium requires the extension of this technique in the receive mode. This paper describes the extension of the matched filter approach in the receive mode and it is shown that optimal focusing in this mode can be achieved using adaptive convolution beamforming techniques instead of simple time delay lines. Theoretical and experimental results are presented to show the efficiency of this technique compared to adaptive delay line focusing.
Understanding the Cardioprotective Effects of Flavonols: Discovery of Relaxant Flavonols without Antioxidant Activity (2008)

3',4'-Dihydroxyflavonol (DiOHF) is a cardioprotective flavonol that can reduce injury after myocardial ischemia and reperfusion and thus is a promising small molecule for the treatment of cardiovascular disease. Like all vasoactive flavonols reported to date, DiOHF is both relaxant and antioxidant, hindering investigation of the relative contribution of each activity for the prevention of reperfusion injury. This study investigates structure-activity relationships of variations at the 3' and 4' positions of the B ring of DiOHF and vasorelaxant and antioxidant activities. Relaxation of rat isolated aortic rings precontracted with KCl revealed that the most active flavonols were those with a 4'-hydroxyl group, with the opening of potassium channels as a possible contributing mechanism. For the antioxidant activity, with the exception of DiOHF, none of the flavonols investigated were able to significantly scavenge superoxide radical, and none of the three most potent vasorelaxant flavonols could prevent oxidant-induced endothelial dysfunction. The discovery of single-acting vasorelaxant flavonols without antioxidant activity, in particular 4'-hydroxy-3'-methoxyflavonol, will assist in investigating the mechanism of flavonol-induced cardioprotection.
Two Functional Coding Single Nucleotide Polymorphisms in STK15 (Aurora-A) Coordinately Increase Esophageal Cancer Risk (2005)

STK15/Aurora-A is a serine/threonine kinase essential for chromosome segregation and cytokinesis, and is considered to be a cancer susceptibility gene in mice and humans. Two coding single nucleotide polymorphisms in Aurora-A, 91T>A [phenylalanine/isoleucine (F/I)] and 169G>A [valine/isoleucine (V/I)], create four haplotypes, 91T-169G, 91A-169G, 91T-169A, and 91A-169A. We evaluated the association between these coding single nucleotide polymorphisms and esophageal cancer risk by genotyping 197 esophageal cancer cases and 146 controls. Haplotype 91A-169A (I31/I57) was observed to be statistically more frequent in cancer cases (odds ratio, 3.1452; 95% confidence interval, 1.0258-9.6435). Functional differences among the four isoforms were then analyzed to reveal the source of the cancer risk. Kinase activity levels of I31/I57 and F31/I57 were reduced to 15% and 40% compared with I31/V57 in vivo and in vitro. We considered the differences between the kinase activities and divided individuals into four categories of Aurora-A haplotype combination. Category I had 57.5% or less kinase activity compared with the most common category, category III, and had a significantly higher estimated cancer risk (odds ratio, 5.5328; 95% confidence interval, 1.8149-16.8671). Abnormal nuclear morphology, a characteristic of genomic instability, was observed to be 30 to 40 times more frequent in human immortalized fibroblast cells overexpressing I31/I57 or F31/I57 compared with the others. Furthermore, significantly higher levels of chromosomal instability were observed in cancers in category I (homozygote 91T-169A) than those in category III (homozygous 91A-169G). These results indicate that the less kinase active Aurora-A haplotype combinations might induce genomic instability and increase esophageal cancer risk either in a recessive or a dominant manner.
Metabolic properties of IgG subclasses in man (1970)

Metabolic properties of the four subclasses of human IgG were investigated by performing 47 turnover studies in individuals with normal IgG serum concentrations, as well as in patients with an increased level of one of the subclasses. Studies in 12 subjects with normal IgG serum concentration showed that the average biologic half-life of G(1), G(2), and G(4) was 21 days, while that of G(3) was only 7.1 days. Fractional catabolic rates of G(1), G(2), and G(4) were 6.9 to 8% of the intravascular pool per day. G(3), however, had a higher fractional catabolic rate, amounting to 16.8% of the intravascular pool per day. Distribution of the subclasses was such that the intravascular compartment contained 51-54% of the total body pools of G(1), G(2), and G(4), but 64% of the total body pool of G(3).The short survival and high fractional catabolic rate of G(3) is an inherent property of these molecules, and is not due to denaturation during isolation and radiolabeling. This was demonstrated by studies of a patient with a serum G(3)-myeloma protein. The survival of her own protein, separately labeled either in vivo with guanidoarginine-(14)C or in vitro with (125)I, was determined in the patient. Survivals of the in vivo and in vitro labeled proteins were identical.G(1) and G(3) serum concentrations and synthetic rates were determined. The mean serum concentration of G(1) was 6.8 mg/ml and that of G(3) was 0.7 mg/ml, while their synthetic rates were 25.4 and 3.4 mg/kg per day respectively. The low serum concentration of IgG(2) thus results from a combination of high catabolic and low synthetic rates. Studies in 10 patients with multiple myeloma showed that an elevated serum concentration of any IgG subclass was associated with shortened biologic half-life and increased fractional catabolic rate of all subclasses. The implications of this concentration-catabolism relationship are discussed. The serum concentration of nonmyeloma IgG was usually low in myeloma patients and the synthesis of nonmyeloma IgG was somewhat decreased, suggesting that low serum concentrations of nonmyeloma IgG result from decreased synthesis, as well as from an increased fractional catabolic rate.
Sensitivity of Noninvasive Prenatal Detection of Fetal Aneuploidy from Maternal Plasma Using Shotgun Sequencing Is Limited Only by Counting Statistics (2010)

We recently demonstrated noninvasive detection of fetal aneuploidy by shotgun sequencing cell-free DNA in maternal plasma using next-generation high throughput sequencer. However, GC bias introduced by the sequencer placed a practical limit on the sensitivity of aneuploidy detection. In this study, we describe a method to computationally remove GC bias in short read sequencing data by applying weight to each sequenced read based on local genomic GC content. We show that sensitivity is limited only by counting statistics and that sensitivity can be increased to arbitrary precision in sample containing arbitrarily small fraction of fetal DNA simply by sequencing more DNA molecules. High throughput shotgun sequencing of maternal plasma DNA should therefore enable noninvasive diagnosis of any type of fetal aneuploidy.
Plasma-Assisted Atomic Layer Growth of High-Quality Aluminum Oxide Thin Films (2001)

Thin aluminum oxide (Al 2 O 3 ) films were grown by the plasma-assisted atomic layer controlled deposition (PAALD) method using Dimethylethylamine alane [(CH 3 ) 2 (C 2 H 5 )N:AlH 3 ] (DMEAA). Al was deposited by the PAALD method, then the Al films were oxidized into Al 2 O 3 by plasma oxidation in the same chamber without breaking the vacuum. Al 2 O 3 thin films of 15 nm thickness were prepared by repetition of this process. Thus prepared Al 2 O 3 thin films exhibited a refractive index of 1.68. The thickness and the refractive index fluctuation of the film over a 4 inch wafer were ±2.3% and ±1.9%, respectively, for the deposited films. The leakage current density and breakdown field were measured to be about 10 -8 A/cm 2 at 1 MV/cm and 7 MV/cm, respectively. Considerable improvement of the electrical properties was realized by the post oxygen-plasma annealing at 200°C.
The disulfide bonds in antibody variable domains: effects on stability, folding in vitro, and functional expression in Escherichia coli (1992)

The formation of the disulfide bonds in the variable domains VH and VL of the antibody McPC603 was found to be essential for the stability of all antigen binding fragments investigated. Exposure of the Fv fragment to reducing conditions in vitro resulted in irreversible denaturation of both VH and VL. In vitro refolding of the reduced Fv fragment was only possible when the disulfide bonds were allowed to form under oxidizing conditions. The analysis of a series of mutants of the Fv fragment, the Fab fragment and the single-chain Fv fragment, all secreted into the periplasm of Escherichia coli, in which each of the cysteine residues of the variable domains was replaced by a series of other amino acids, showed that functional antigen binding fragments required the presence of both the disulfide bond in VH and the one in VL. These results were also used to devise an alternative expression system based on the production of insoluble fusion proteins consisting of truncated beta-galactosidase and antibody domains, enzymatic cleavage, and refolding and assembly in vitro. This strategy should be useful for providing access to unstable antibody domains and fragments.
Role of S-adenosyl-l-methionine in the treatment of depression: a review of the evidence,,, (2002)

Major depression remains difficult to treat, despite the wide array of registered antidepressants available. In recent years there has been a surge in the popularity of natural or alternative medications. Despite this growing popularity, there is limited evidence for the effectiveness of many of these natural treatments. S-adenosyl-L-methionine (SAMe) is one of the better studied of the natural remedies. SAMe is a methyl donor and is involved in the synthesis of various neurotransmitters in the brain. Derived from the amino acid L-methionine through a metabolic pathway called the one-carbon cycle, SAMe has been postulated to have antidepressant properties. A small number of clinical trials with parenteral or oral SAMe have shown that, at doses of 200-1600 mg/d, SAMe is superior to placebo and is as effective as tricyclic antidepressants in alleviating depression, although some individuals may require higher doses. SAMe may have a faster onset of action than do conventional antidepressants and may potentiate the effect of tricyclic antidepressants. SAMe may also protect against the deleterious effects of Alzheimer disease. SAMe is well tolerated and relatively free of adverse effects, although some cases of mania have been reported in bipolar patients. Overall, SAMe appears to be safe and effective in the treatment of depression, but more research is needed to determine optimal doses. Head-to-head comparisons with newer antidepressants should help to clarify SAMe's place in the psychopharmacologic armamentarium.
The function of the soluble interleukin 6 (IL-6) receptor in vivo: sensitization of human soluble IL-6 receptor transgenic mice towards IL-6 and prolongation of the plasma half-life of IL-6. (1996)

Interleukin 6 (IL-6) is considered an important mediator of acute inflammatory responses. Moreover, IL-6 functions as a differentiation and growth factor of hematopoietic precursor cells, B cells, T cells, keratinocytes, neuronal cells, osteoclasts, and endothelial cells. IL-6 exhibits its action via a receptor complex consisting of a specific IL-6 receptor (IL-6R) and a signal transducing subunit (gp130). Soluble forms of both receptor components are generated by shedding and are found in patients with various diseases such as acquired immune deficiency syndrome, rheumatoid arthritis, and others. The function of the soluble (s)IL-6R in vivo is unknown. Since human (h)IL-6 acts on human and murine target cells, but murine IL-6 on murine cells only, we constructed transgenic mice expressing the hsIL-6R. We report here that in the presence of hsIL-6R, mice are hypersensitized towards hIL-6, mounting an acute phase protein gene induction at significantly lower IL-6 dosages compared to control animals. Furthermore, in hsIL-6R transgenic mice, the detected acute phase response persists for a longer period of time. The IL-6/IL-6R complex prolongs markedly the Il-6 plasma half-life. Our results reinforce the role of the hsIL-6R as an agonistic protein, help to understand the function of the hsIL-6R in vivo, and highlight the significance of the receptor in the induction of the acute phase response.
Animal Models of Tumor-Suppressor Genes (2001)

The development of cancer requires multiple genetic alterations perturbing distinct cellular pathways. In human cancers, these alterations often arise owing to mutations in tumor-suppressor genes whose normal function is to either inhibit the proliferation, apoptosis, or differentiation of cells, or maintain their genomic integrity. Mouse models for tumor suppressors frequently provide definitive evidence for the antitumorigenic functions of these genes. In addition, animal models permit the identification of previously unsuspected roles of these genes in development and differentiation. The availability of null and tissue-specific mouse mutants for tumor-suppressor genes has greatly facilitated our understanding of the mechanisms leading to cancer. In this review, we describe mouse models for tumor-suppressor genes.
Retinal Ganglion Cell Life and Death – Mechanisms and Implications for Ophthalmology (2009)

Retinal ganglion cell (RGC) survival is critical for vision, but these neurons are exquisitely sensitive to insults. In acute diseases such as ischaemic optic neuropathy or optic neuritis, or in chronic diseases such as glaucoma, injury to RGC axons in the optic nerve may lead to rapid RGC death. Retinal ischaemia and retinal artery or vein occlusions directly injure RGC cell bodies in the ganglion cell layer. Enhancing RGC viability (neuroprotection) or RGC function (neuroenhancement) remains a major goal of basic and translational research. In this article we review the many mechanisms that lead from such insults to RGC death in clinically relevant pathological processes, and discuss avenues being pursued to enhance RGC survival in human disease.
Comparison of the Effects of Various C-Terminal and NTerminal Fragment Peptides of Glucagon-Like Peptide-1 on Insulin and Glucagon Release from the Isolated Perfused Rat Pancreas* (1989)

Truncated glucagon-like peptide-1 (GLP-1) possesses a potent stimulatory activity for insulin secretion and a slight inhibiting activity for glucagon secretion. The aim of this paper is to examine the activities of N- and C-terminal fragments of GLP-1 using a rat pancreas perfusion system. Concerning the N-terminal portion, GLP-1(7-37) amide elicited a clear insulinotropic activity at 0.1 or 1 nM with the perfusate containing 5.5 mM glucose and 5 mM arginine, while 10 nM GLP-1-(1-37) amide, -(6-37) amide, and -(8-37) amide did not. Concerning the C-terminal portion, GLP-1-(7-37) amide, -(7-37), and -(7-36) amide had a similar potency of insulinotropic activity, and GLP-1-(7-35) was less potent; 0.1 nM GLP-1-(7-35) did not stimulate insulin release, nor did 10 nM GLP-1-(7-20). Glucagon release was significantly suppressed by 1 and 10 nM GLP-1-(7-37) amide, 10 nM GLP-1-(7-37), and 1 nM GLP-1-(7-36) amide. Other fragment peptides of GLP-1, including GLP-1-(7-35), had no effect. From these results it is concluded that histidine at position 7 of GLP-1 as a free N-terminal amino acid is very important in GLP-1's insulinotropic activity and probably in glucagon-inhibiting activity, and that C-terminal amidation and three C-terminal amino acids are less important for these activities.
Selective cyclin-dependent kinase 2/cyclin A antagonists that differ from ATP site inhibitors block tumor growth. (2003)

A central function of the tumor suppressor retinoblastoma (Rb) is its ability to repress E2F transcriptional activity. Many cancers harbor inactivated Rb and consequently deregulated E2F. RXL peptides inhibit E2F recruitment and phosphorylation by CDK2/cyclin A. Here we report that RXL peptides selectively kill tumor cells with deregulated Rb/cyclin D pathways. We extend these observations to tumor models and demonstrate inhibition of tumor growth in SV40 large T transformed Balb/c 3T3 grafts and in HER2 transgenic tumors. Moreover, our observations reveal that RXL peptide-treated tumors undergo apoptosis. Our results indicate that RXL motif-based inhibitors will provide selective antiproliferative agents with in vivo efficacy in tumors with deregulated Rb/cyclin D pathways.
Myoelectric Signal Processing: Optimal Estimation Applied to Electromyography - Part I: Derivation of the Optimal Myoprocessor (1980)

This paper (Part I of II) describes the development of a novel technique for processing the electrical activity of muscle which uses multiple channels of myoelectric activity. A phenomenological mathematical model of myoelectric activity is formulated. From this model, a mathematical statement of the optimal myoelectric signal processor is derived, and some of its properties are investigated. This mathematical statement encompasses and places in perspective almost all single-channel myoprocessor developments to date, as well as specifying the optimal multiple-channel myoprocessor. An experimental demonstration of the efficacy of this processor is presented in a subsequent paper (Part II).
Further studies on the reaction of disulphides with silver nitrate (1957)

Research Article| July 01 1957 Further studies on the reaction of disulphides with silver nitrate R. Cecil; R. Cecil 1Department of Biochemistry, University of Oxford Search for other works by this author on: This Site PubMed Google Scholar J. R. McPhee J. R. McPhee 1Department of Biochemistry, University of Oxford Search for other works by this author on: This Site PubMed Google Scholar Biochem J (1957) 66 (3): 538–543. https://doi.org/10.1042/bj0660538 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn Email Cite Icon Cite Get Permissions Citation R. Cecil, J. R. McPhee; Further studies on the reaction of disulphides with silver nitrate. Biochem J 1 July 1957; 66 (3): 538–543. doi: https://doi.org/10.1042/bj0660538 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsBiochemical Journal Search Advanced Search © 1957 CAMBRIDGE UNIVERSITY PRESS1957 Article PDF first page preview Close Modal You do not currently have access to this content.
Quantitative and Qualitative Changes in V-J α Rearrangements During Mouse Thymocytes Differentiation (2002)

Knowledge of the complete nucleotide sequence of the mouse TCRAD locus allows an accurate determination V-J rearrangement status. Using multiplex genomic PCR assays and real time PCR analysis, we report a comprehensive and systematic analysis of the V-J recombination of TCR alpha chain in normal mouse thymocytes during development. These respective qualitative and quantitative approaches give rise to four major points describing the control of gene rearrangements. (a) The V-J recombination pattern is not random during ontogeny and generates a limited TCR alpha repertoire; (b) V-J rearrangement control is intrinsic to the thymus; (c) each V gene rearranges to a set of contiguous J segments with a gaussian-like frequency; (d) there are more rearrangements involving V genes at the 3' side than 5' end of V region. Taken together, this reflects a preferential association of V and J gene segments according to their respective positions in the locus, indicating that accessibility of both V and J regions is coordinately regulated, but in different ways. These results provide a new insight into TCR alpha repertoire size and suggest a scenario for V usage during differentiation.
Perceptrons (2017)

The first systematic study of parallelism in computation by two pioneers in the field. Reissue of the 1988 Expanded Edition with a new foreword by Léon Bottou In 1969, ten years after the discovery of the perceptron—which showed that a machine could be taught to perform certain tasks using examples—Marvin Minsky and Seymour Papert published Perceptrons, their analysis of the computational capabilities of perceptrons for specific tasks. As Léon Bottou writes in his foreword to this edition, “Their rigorous work and brilliant technique does not make the perceptron look very good.” Perhaps as a result, research turned away from the perceptron. Then the pendulum swung back, and machine learning became the fastest-growing field in computer science. Minsky and Papert's insistence on its theoretical foundations is newly relevant. Perceptrons—the first systematic study of parallelism in computation—marked a historic turn in artificial intelligence, returning to the idea that intelligence might emerge from the activity of networks of neuron-like entities. Minsky and Papert provided mathematical analysis that showed the limitations of a class of computing machines that could be considered as models of the brain. Minsky and Papert added a new chapter in 1987 in which they discuss the state of parallel computers, and note a central theoretical challenge: reaching a deeper understanding of how “objects” or “agents” with individuality can emerge in a network. Progress in this area would link connectionism with what the authors have called “society theories of mind.”