gebhart/patrepeval huggingface dataset:
The highly attenuated vaccinia virus strain modified virus Ankara induces apoptosis in melanoma cells and allows bystander dendritic cells to generate a potent anti-tumoral immunity (2006)

Vaccinia virus (VV) has been tested as oncolytic virus against malignant melanoma in clinical trials for more than 40 years. Until now, mainly strains comparable to viral strains used for smallpox vaccination have been probed for anti-tumoral therapy. We have shown recently that the wild-type strain Western Reserve (WR) can interfere with crucial functions of monocyte-derived dendritic cells (DCs). Our aim was to examine whether viral immune evasion mechanisms might be responsible for the ineffectiveness of WR-based vaccination strategies and whether the highly attenuated strain modified virus Ankara (MVA) differs from WR with respect to its possible immunostimulatory capacity after intratumoral injection. Using in vitro experiments, we compared the effect of both strains on melanoma cells and on local bystander DCs. We found that both VV-strains infected melanoma cells efficiently and caused disintegration of the actin cytoskeleton, as shown by fluorescence microscopy. In addition, both VV-strains caused apoptotic cell death in melanoma cells after infection. In contrast to MVA, WR underwent a complete viral replication cycle in melanoma cells. Bystander DCs were consecutively infected by newly generated WR virions and lost their capacity to induce allogeneic T cell proliferation. DCs in contact with MVA-infected melanoma cells retained their capacity to induce T cell proliferation. Immature DCs were capable of phagocytosing MVA-infected melanoma cells. Priming of autologous CD8(+) T cells by DCs that had phagocytosed MVA-infected, MelanA positive melanoma cells resulted in the induction of T cell clones specifically reactive against the model antigen MelanA as shown by enzyme-linked immunospot (ELISPOT) analysis. We conclude that the clinical trials with oncolytic wild-type VV failed probably because of suppression of bystander DCs and consecutive suppression of T cell-mediated anti-melanoma immunity. The attenuated VV-strain MVA facilitates the generation of tumour associated antigen (TAA)-specific T cell response as it is oncolytic for melanoma cells, but non-toxic for DC, and should be a promising candidate for intralesional metastatic melanoma therapy.
Cetuximab in metastatic colorectal cancer (2012)

Management of metastatic colorectal cancer has evolved in the last 10 years, with the availability of targeted therapies resulting in improvement in quality of life and overall survival. Cetuximab is a chimeric monoclonal antibody that binds to the EGF receptor, and the net effects are inhibition of tumor growth, invasion, angiogenesis and metastasis. Cetuximab binding to the EGF receptor is also known to augment the effects of chemotherapy and radiotherapy. Only tumors expressing wild-type KRAS respond to cetuximab and improvements in progression-free survival and overall survival are seen, whereas patients with mutant KRAS are considered to be resistant. Cetuximab is currently available worldwide for use as monotherapy or in combination with chemotherapy in first-, second- or third-line settings in metastatic colorectal cancer patients with wild-type KRAS.
Emodin, a Protein Tyrosine Kinase Inhibitor from Polygonum cuspidatum (1992)

Bioassay-directed fractionation of a Chinese medicinal plant, Polygonum cuspidatum (Polygonaceae), has led to the discovery of an anthraquinone, emodin [1], as a strong inhibitor of a protein tyrosine kinase (p56lck) partially purified from bovine thymus. Comparison of the IC50 values of emodin for protein tyrosine kinase inhibitory activity with physcion [2] and emodin-O8-D-glucoside [3], also isolated from the same plant, reveal the importance of the hydroxyl groups at C-6 and C-8 for the observed activity.
A family of genes encoding neurotransmitter transporters. (1992)

The genomic and cDNA clones of the mouse gamma-aminobutyric acid transporter were sequenced and analyzed. The genomic clone contains 12 introns including 1 intron prior to the initiator methionine. The second intron comes immediately after the stretch of amino acids that is most conserved among the neurotransmitter transporters sequenced so far. By using a probe constructed according to this conserved region, several partial genomic clones were isolated. Sequence analysis of those clones reveals not only homology to the family of neurotransmitter transporters within the reading frame but also an identical location of an exon-intron junction after the conserved region. A search of the GenBank data base (April 1991) revealed that two invertebrate genes exhibit homology to the conserved sequence of the above family. One, a Drosophila melanogaster gene, encoded the N-terminal part of a protein homologous to neurotransmitter transporters and the second was in Caenorhabditis elegans. The Drosophila gene contains an intron that starts at a position identical to the corresponding positions of all the mammalian genes of the family.
Local and Systemic Effects of Intradermal Recombinant Interferon-γ in Patients with Lepromatous Leprosy (1986)

Evidence that interferon-gamma may be a physiologic macrophage-activating factor, and that macrophage activation may be defective in lepromatous leprosy, led us to test the effects of intradermal injection of low doses of recombinant interferon-gamma in six patients with this disease. Interferon-gamma, 1 or 10 micrograms, was administered daily by jet gun for three days into a single cutaneous lesion. A biopsy specimen was taken from the injection site on the sixth study day and compared with specimens obtained previously from a site where no injection had been made or where excipient alone had been injected in the same way as the interferon. Interferon-gamma elicited local effects similar to certain features of delayed-type hypersensitivity reactions or tuberculoid leprosy, including induration, T-cell and monocyte infiltration, keratinocyte proliferation, diminution of epidermal Langerhans cells, and dermal and epidermal cell HLA-DR (Ia) antigen expression. At some of the sites of interferon-gamma injection, there was also an apparent decrease in acid-fast bacilli. Before treatment, monocytes from patients with lepromatous leprosy released 48 percent as much hydrogen peroxide as did monocytes from controls in response to phorbol myristate acetate, and 36 percent as much as those from controls in response to Mycobacterium leprae. When recombinant interferon-gamma was injected, these responses became normal. No toxic effects were observed. These observations suggest that interferon-gamma can mediate certain manifestations of delayed-type hypersensitivity or cell-mediated immunity in vivo, and that recombinant interferon-gamma should be tested for possible therapeutic effects in certain nonviral infectious diseases.
Hydride-mediated homogeneous catalysis. Catalytic reduction of .alpha.,.beta.-unsaturated ketones using [(Ph3P)CuH]6 and H2 (1989)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTHydride-mediated homogeneous catalysis. Catalytic reduction of .alpha.,.beta.-unsaturated ketones using [(Ph3P)CuH]6 and H2Wayne S. Mahoney and Jeffrey M. StrykerCite this: J. Am. Chem. Soc. 1989, 111, 24, 8818–8823Publication Date (Print):November 1, 1989Publication History Published online1 May 2002Published inissue 1 November 1989https://pubs.acs.org/doi/10.1021/ja00206a008https://doi.org/10.1021/ja00206a008research-articleACS PublicationsRequest reuse permissionsArticle Views2933Altmetric-Citations172LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
Inhibition of PDE4B suppresses inflammation by increasing expression of the deubiquitinase CYLD (2013)

The deubiquitinase CYLD acts as a key negative regulator to tightly control overactive inflammation. Most anti-inflammatory strategies have focused on directly targeting the positive regulator, which often results in significant side effects such as suppression of the host defence response. Here, we show that inhibition of phosphodiesterase 4B (PDE4B) markedly enhances upregulation of CYLD expression in response to bacteria, thereby suggesting that PDE4B acts as a negative regulator for CYLD. Interestingly, in Cyld-deficient mice, inhibition of PDE4B no longer suppresses inflammation. Moreover, PDE4B negatively regulates CYLD via specific activation of JNK2 but not JNK1. Importantly, ototopical post-inoculation administration of a PDE4 inhibitor suppresses inflammation in this animal model, thus demonstrating the therapeutic potential of targeting PDE4. These studies provide insights into how inflammation is tightly regulated via the inhibition of its negative regulator and may also lead to the development of new anti-inflammatory therapeutics that upregulate CYLD expression.
La convergence constitue-elle le seul critère d’évaluation de la politique européenne de cohésion économique et sociale (2010)

La politique européenne de cohésion visant à réduire les disparités régionales est-elle efficace ? On peut en douter. Dans l'UE à 15 les écarts de développement interrégionaux mesurés par le PIB /habitant restaient significatifs. A la suite de l'élargissement ils ont pratiquement doublé. Le principal critère est constitué par une mesure de la convergence. Les analyses empiriques sont unanimement pessimistes et montrent que la convergence est au mieux très lente et au pire une vue de l'esprit. Faut-il pour autant renoncer à la politique régionale ? Les effets positifs de la politique européenne sur les initiatives régionales et l'entrée de l'Europe dans une économie de la connaissance laissent penser que la convergence n'est désormais plus le seul critère d'appréciation.
Use of synthetic oligopeptides in identification and characterization of immunological functions in the amino acid sequence of the envelope protein of HIV-1 (1989)

Following computer-assisted analysis of the amino acid sequence of various HIV-1 isolates, we synthesized a series of oligopeptides derived from variable and conserved regions of the envelope protein complex gp120/gp41. The peptides were used in ELISA tests for their reactivity with human antisera from HIV-1 positive individuals; patients with clinically manifested AIDS showed only a rather limited reaction, predominantly with two peptides (p102-112, p316-326), which is in contrast to sera from HIV-1 positive asymptomatic individuals, whose sera were reactive with almost all peptides. Using consecutive sera of the same patients, decreasing antibody titers to defined epitopes could be shown to occur during the development of AIDS. Cellular immune response recognition was analyzed in T-cell proliferation assays by [3H]thymidine incorporation. One peptide localized in a conserved region clearly induced proliferation of T-cells. Those data were combined to a map of the functions localized in the various regions of the HIV-1 envelope proteins.
Object management system concepts (1984)

An office database should be a “total” information resource in that it should be capable of storing data of many arbitrary types. Users of such a system should be able to store conveniently their documents and graphics objects in the same logical storage space as their more traditional records-oriented data.
Matrix metalloproteinases: structures, evolution, and diversification (1998)

A comprehensive sequence alignment of 64 members of the family of matrix metalloproteinases (MMPs) for the entire sequences, and subsequently the catalytic and the hemopexin-like domains, have been performed. The 64 MMPs were selected from plants, invertebrates, and vertebrates. The analyses disclosed that as many as 23 distinct subfamilies of these proteins are known to exist. Information from the sequence alignments was correlated with structures, both crystallographic as well as computational, of the catalytic domains for the 23 representative members of the MMP family. A survey of the metal binding sites and two loops containing variable sequences of amino acids, which are important for substrate interactions, are discussed. The collective data support the proposal that the assembly of the domains into multidomain enzymes was likely to be an early evolutionary event. This was followed by diversification, perhaps in parallel among the MMPs, in a subsequent evolutionary time scale. Analysis indicates that a retrograde structure simplification may have accounted for the evolution of MMPs with simple domain constituents, such as matrilysin, from the larger and more elaborate enzymes.
An overview of genetic algorithms: Part 1, fundamentals (1993)

Genetic Algorithms (GAs) are adaptive methods which may be used to solve search and optimisation problems. They are based on the genetic processes of biological organisms. Over many generations, natural populations evolve according to the principles of natural selection and \survival of the ttest, rst clearly stated by Charles Darwin in The Origin of Species. By mimicking this process, genetic algorithms are able to \evolve solutions to real world problems, if they have been suitably encoded. For example, GAs can be used to design bridge structures, for maximum strength/weight ratio, or to determine the least wasteful layout for cutting shapes from cloth. They can also be used for online process control, such as in a chemical plant, or load balancing on a multi-processor computer system. The basic principles of GAs were rst laid down rigourously by Holland [Hol75], and are well described in many texts (e.g. [Dav87, Dav91, Gre86, Gre90, Gol89a, Mic92]). GAs simulate those processes in natural populations which are essential to evolution. Exactly which biological processes are essential for evolution, and which processes have little or no role to play is still a matter for research; but the foundations are clear. In nature, individuals in a population compete with each other for resources such as food, water and shelter. Also, members of the same species often compete to attract a mate. Those individuals which are most successful in surviving and attracting mates will have relatively larger numbers of o spring. Poorly performing individuals will produce few of even no o spring at all. This means that the genes from the highly adapted, or individuals will spread to an increasing number of individuals in each successive generation. The combination of good characteristics from di erent ancestors can sometimes produce \super o spring, whose tness is greater than that of either parent. In this way, species evolve to become more and more well suited to their environment. GAs use a direct analogy of natural behaviour. They work with a population of \individuals, each representing a possible solution to a given problem. Each individual is assigned a tness according to how good a solution to the problem it is. For example, the tness score might be the strength/weight ratio for a given bridge design. (In nature this is equivalent to assessing how e ective an organism is at competing for resources.) The highly t individuals are given opportunities to \reproduce, by \cross breeding with other
Narrowband to wideband conversion of speech using GMM based transformation (2002)

Reconstruction of wideband speech from its narrowband version is an attractive issue, since it can enhance the speech quality without modifying the existing communication networks. This paper proposes a new recovery method of wideband speech from narrowband speech. In the proposed method, the narrowband spectral envelope of input speech is transformed to a wideband spectral envelope based on the Gaussian mixture model (GMM), whose parameters are calculated by a joint density estimation technique. Then the lowband and highband speech signal is reconstructed by the LPC synthesizer using the reconstructed spectral envelope. This paper also proposes a codeword-dependent power estimation method. Both the objective and subjective test results shows that the proposed algorithm outperforms the conventional codebook mapping method.
Laser Angioplasty and Intracoronary Stents: Going Beyond the Balloon (1994)

Laser angioplasty and balloon-expandable intracoronary stenting are two valuable clinical devices that are now used in interventional cardiology. The description, rationale, and clinical application of each device are examined to enhance the nurse's understanding of intervention choices. Primary nursing diagnoses are described, and special nursing considerations are discussed to aid the critical-care nurse in assessing patient needs, monitoring therapies, optimizing care, and being a mediator of stress between the patient and new technology.
Blunt Trauma of the Aging Eye (2005)

On the basis of the computational modeling analysis, the risk of eye injury increases with age; as a result, the eyes of elderly patients may be more susceptible to ciliary body-related eye injuries in traumatic-impact situations. Clinical Relevance These data support the contention that trauma-induced damage to the lens, ciliary body, and zonules may be related to increased stiffness of the lens. The data indicate that all people, especially elderly individuals, should use safety systems while driving an automobile and sit as far from the air bag as is comfortable. Those in sports or work environments requiring protective lenses should wear them. Designers of air bags and automobile companies should continue to work to reduce the potential that the air bag will contact the eye.
Non-transitive connectivity and DHTs (2005)

The most basic functionality of a distributed hash table, or DHT, is to partition a key space across the set of nodes in a distributed system such that all nodes agree on the par-titioning. For example, the Chord DHT assigns each node
Alcaptonuria and ochronotic arthritis. (1991)

The rare hereditary metabolic disorder alcaptonuria is characterized by the inability to metabolize homogentisic acid, an intermediary compound in the catabolism of the aromatic amino acids phenylalanine and tyrosine. The essentially complete deficiency of homogentisic acid oxidase causes a striking accumulation of homogentisic acid and a derived melanin-like pigment in the connective tissues; the latter is termed ochronosis. Urinary homogentisic acid is oxidized rapidly and becomes a brown or black pigment if alkali is added. Older alcaptonurics have intensely pigmented (ochronotic) connective tissues, primarily the cartilaginous joint surfaces, ribs, intervertebral disks, ear cartilage, etc. They also have an unusual type of arthritis affecting the large weight-bearing joints, i.e. hips, knees and spine, but not the small joints of the hands and feet, as in rheumatoid arthritis. A mechanistic explanation for ochronotic arthritis has not been worked out, but it is clear that accumulation of homogentisic acid in the connective tissues directly or indirectly leads to the arthritic changes. A detailed analysis of the events leading to alcaptonuric arthritis should be worthwhile since it is a model form of arthritis secondary to a well-defined metabolic disorder that must persist for many years before the arthritic complications appear. Possibly other, more common types of arthritis, develop secondarily to metabolic disturbances that involve chemical mediators less obvious, or less easily detected, than homogentisic acid.
Design and use of multi‐affinity surfaces in biomolecular interaction analysis–mass spectrometry (BIA/MS): a step toward the design of SPR/MS arrays (2003)

The feasibility of multi-affinity ligand surfaces in biomolecular interaction analysis-mass spectrometry (BIA/MS) was explored in this work. Multi-protein affinity surfaces were constructed by utilizing antibodies to beta-2-microglobulin, cystatin C, retinol binding protein, transthyretin, serum amyloid P and C-reactive protein. In the initial experiments, all six antibodies were immobilized on a single site (flow cell) on the sensor chip surface, followed by verification of the surface activity via separate injections of purified proteins. After an injection of diluted human plasma aliquot over the antibodies-derivatized surfaces, and subsequent MALDI-TOF MS analysis, signals representing five out of the six targeted proteins were observed in the mass spectra. Further, to avoid the complexity of the spectra, the six proteins were divided into two groups (according to their molecular weight) and immobilized on two separate surfaces on a single sensor chip, followed by an injection of human plasma aliquot. The resulting mass spectra showed signals from all proteins. Also, the convolution resulting from the multiply charged ion species was eliminated. The ability to create such multi-affinity surfaces indicates that smaller-size ligand areas/spots can be employed in the BIA/MS protein interaction screening experiments, and opens up the possibilities for construction of novel multi-arrayed SPR-MS platforms and methods for high-throughput parallel protein interaction investigations.
Absorption and excretion of radioactively tagged dextroamphetamine sulfate from a sustained-release preparation. (1965)

This study was undertaken to test the reliability of a sustained-release dosage form of dextroamphetamine sulfate. We tagged the drug with the radioactive carbon atom and gave four dosage regimens to 16 subjects following an incomplete block crossover design. The plasma and urine data obtained showed that the 15-mg sustained-release dosage form tested performed in a way comparable to 5 mg given three times each day, that it released its drug over a prolonged period, and that it was equivalent to other 15-mg regimens in the amount of drug made available for absorption. On the basis of these findings, we can say that the sustainedrelease dosage form tested is a reliable way to administer dextroamphetamine sulfate. The tests described herein, and tests of similar complexity, are becoming a more and more essential part of the evaluation of such dosage forms.