gebhart/patrepeval huggingface dataset:
Cholecystokinin antagonists: Pharmacological and therapeutic potential (2003)

Cholecystokinin (CCK) is a regulatory peptide hormone, predominantly found in the gastrointestinal tract, and a neurotransmitter present throughout the nervous system. In the gastrointestinal system CCK regulates motility, pancreatic enzyme secretion, gastric emptying, and gastric acid secretion. In the nervous system CCK is involved in anxiogenesis, satiety, nociception, and memory and learning processes. Moreover, CCK interacts with other neurotransmitters in some areas of the CNS. The biological effects of CCK are mediated by two specific G protein coupled receptor subtypes, termed CCK(1) and CCK(2). Over the past fifteen years the search of CCK receptor ligands has evolved from the initial CCK structure derived peptides towards peptidomimetic or non-peptide agonists and antagonists with improved pharmacokinetic profile. This research has provided a broad assortment of potent and selective CCK(1) and CCK(2) antagonists of diverse chemical structure. These antagonists have been discovered through optimization programs of lead compounds which were designed based on the structures of the C-terminal tetrapeptide, CCK-4, or the non-peptide natural compound, asperlicin, or derived from random screening programs. This review covers the main pharmacological and therapeutic aspects of these CCK(1) and CCK(2) antagonist. CCK(1) antagonists might have therapeutic potential for the treatment of pancreatic disorders and as prokinetics for the treatment of gastroesophageal reflux disease, bowel disorders, and gastroparesis. On the other hand, CCK(2) antagonists might have application for the treatment of gastric acid secretion and anxiety disorders.
Phase‐sensitive sodium B1 mapping (2010)

Quantitative sodium MRI requires accurate knowledge of factors affecting the sodium signal. One important determinant of sodium signal level is the transmit B(1) field strength. However, the low signal-to-noise ratio typical of sodium MRI makes accurate B(1) mapping in reasonable scan times challenging. A new phase-sensitive B(1) mapping technique has recently been shown to work better than the widely used dual-angle method in low-signal-to-noise ratio situations and over a broader range of flip angles. In this work, the phase-sensitive B(1) mapping technique is applied to sodium, and its performance compared to the dual-angle method through both simulation and phantom studies. The phase-sensitive method is shown to yield higher quality B(1) maps at low signal-to-noise ratio and greater consistency of measurement than the dual-angle method. An in vivo sodium B(1) map of the human breast is also shown, demonstrating the phase-sensitive method's feasibility for human studies.
In vitro Derby Imaging of Cancer Biomarkers Using Quantum Dots (2009)

Semiconductor quantum dots (QDs), which have broad absorption with narrow emission spectra, are useful for multiplex imaging. Here, fluorescence derby imaging using dual color QDs conjugated by the AS1411 aptamer (targeting nucleolin) and the arginine-glycine-aspartic acid (targeting the integrin alpha(v)beta(3)) in cancer cells is reported. Simultaneous fluorescence imaging of cellular distribution of nucleolin and integrin alpha(v)beta(3) using QDs enables easy monitoring of separate targets in the cancer cells and the normal healthy cells. These results suggest the feasibility of a concurrent visualization of QD-based multiple cancer biomarkers using small molecules such as aptamer or peptide ligands.
Distribution of minor collagens during skin development (1997)

The skin is a tissue containing a large number of collagen types. Several collagens are restricted at the dermo-epidermal junction, contrarily to others present throughout the dermis. However, the distribution of the dermal collagen varies during embryonic development. In this contribution, we have been interested in the collagen types associated with the major collagenous components of the dermis, which are the collagen types I and III. Type V collagen, which is mixed with collagen types I and III to form heterotypic fibrils, has been studied during mouse embryo development. Transcripts of the α1(V) gene have been localized by in situ hybridization, on flattened cells of the stratum germinativum first, and then only on dermal cells. The expression of the gene decreases at birth, while the expression of the α1(I) gene remains constant, with, however, a ring of high intensity around hair follicles. Other collagen types (VI, and the fibril-associated collagens XII and XIV) have been studied during calf embryonic development by immunofluorescence and ultrastructural immunogold detection. Type VI collagen appears homogeneously distributed throughout the dermis. Type XII collagen is first widely distributed and becomes restricted in the upper, papillary dermis after 6 months of gestation. Type XIV collagen, on the contrary, is first located as a delicate framework around hair follicles (at 19 weeks of gestation), and progressively invades the whole dermis where it appears abundant just before birth. The different functions of all these collagens are discussed in terms of dermis architecture, mechanical properties and physiology. Microsc. Res. Tech. 38:407–412, 1997. © 1997 Wiley-Liss, Inc.
A selective sphingosine kinase 1 inhibitor integrates multiple molecular therapeutic targets in human leukemia (2008)

The potent bioactive sphingolipid mediator, sphingosine-1-phosphate (S1P), is produced by 2 sphingosine kinase isoenzymes, SphK1 and SphK2. Expression of SphK1 is up-regulated in cancers, including leukemia, and associated with cancer progression. A screen of sphingosine analogs identified (2R,3S,4E)-N-methyl-5-(4'-pentylphenyl)-2-aminopent-4-ene-1,3-diol, designated SK1-I (BML-258), as a potent, water-soluble, isoenzyme-specific inhibitor of SphK1. In contrast to pan-SphK inhibitors, SK1-I did not inhibit SphK2, PKC, or numerous other protein kinases. SK1-I decreased growth and survival of human leukemia U937 and Jurkat cells, and enhanced apoptosis and cleavage of Bcl-2. Lethality of SK1-I was reversed by caspase inhibitors and by expression of Bcl-2. SK1-I not only decreased S1P levels but concomitantly increased levels of its proapoptotic precursor ceramide. Conversely, S1P protected against SK1-I-induced apoptosis. SK1-I also induced multiple perturbations in activation of signaling and survival-related proteins, including diminished phosphorylation of ERK1/2 and Akt. Expression of constitutively active Akt protected against SK1-I-induced apoptosis. Notably, SK1-I potently induced apoptosis in leukemic blasts isolated from patients with acute myelogenous leukemia but was relatively sparing of normal peripheral blood mononuclear leukocytes. Moreover, SK1-I markedly reduced growth of AML xenograft tumors. Our results suggest that specific inhibitors of SphK1 warrant attention as potential additions to the therapeutic armamentarium in leukemia.
A distributed trust model (1997)

Article A distributed trust model Share on Authors: Alfarez Abdul-Rahman Department of Computer Science, University College London, Gower Street, London WC1E 6BT, United Kingdom Department of Computer Science, University College London, Gower Street, London WC1E 6BT, United KingdomView Profile , Stephen Hailes Department of Computer Science, University College London, Gower Street, London WC1E 6BT, United Kingdom Department of Computer Science, University College London, Gower Street, London WC1E 6BT, United KingdomView Profile Authors Info & Claims NSPW '97: Proceedings of the 1997 workshop on New security paradigmsJanuary 1998 Pages 48–60https://doi.org/10.1145/283699.283739Online:01 January 1998Publication History 377citation5,976DownloadsMetricsTotal Citations377Total Downloads5,976Last 12 Months250Last 6 weeks42 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my AlertsNew Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteGet Access
Fixation of C' and C'la by rabbit gamma-G- and gamma-M-antibodies with particulate and soluble antigens. (1968)

Summary C′ and C′1a fixation by γG- and γM-antibodies was studied with A substance and type A human erythrocytes as antigens and specifically purified rabbit antibodies. In soluble antigen systems, the maximal C′ fixation by γG-antibody was obtained at the equivalence antigen to antibody ratio, whereas the maximal fixation by γM-antibody was obtained in excess antibody. At the optimal antigen to antibody ratio for C′ fixation, the C′-fixing activity of the γG- and γM-antibodies was comparable on a molar basis. Essentially no C′ fixation was observed by soluble antigen-γM-antibody complexes formed in excess antigen. Comparisons of C′1a fixation by γG- and γM-antibodies in both soluble and cell antigen systems indicated that γM-antibody is more effective than γG-antibody on the cell surface, while the effect was reversed when the soluble antigen was used. It was confirmed that a single γM-antibody molecule on the cell surface established one C′1a-fixing site. The γM-antibody complexes with insoluble A substance had much higher C′ and C′1a-fixing activities than those combined with soluble A substance. The different efficiency of C′1a fixation by γM-antibody, depending on the nature of antigen, was ascribed to the number and distribution of antigenic determinants on the surface of antigen involved. The results strongly suggested that a combination of γM-antibody molecules with antigen through multiple combining sites is essential for the induction of C′-fixing activity by γM-antibody.
Exosomes Derived from Genetically Modified DC Expressing FasL Are Anti-inflammatory and Immunosuppressive (2005)

We previously have demonstrated the ability of primary murine bone marrow-derived DC (BM-DC), genetically modified by adenoviral infection to express FasL, to inhibit progression of established collagen-induced arthritis (CIA) following systemic delivery. Here we demonstrate that exosomes derived from genetically modified BM-DC expressing FasL are able to inhibit inflammation in a murine footpad model of delayed-type hypersensitivity (DTH). Local administration of exosomes derived from DC expressing FasL (Exo/FasL) as well as the parental DC/FasL resulted in a significant reduction in swelling in both the treated and the untreated distal paw. However, both the DC/FasL and the Exo/FasL were unable to suppress the DTH response in lpr (Fas-deficient) mice. Gene transfer of FasL to BM-DC from gld (FasL-deficient) mice resulted in restoration of the ability of DC as well as DC-derived exosomes to suppress DTH. The ability of DC-derived exosomes and DC to suppress DTH responses was antigen specific and MHC class II dependent, but class I independent. The injected exosomes were found to be internalized into CD11c(+) cells at the site of injection and in the draining popliteal lymph node. Systemic injection of exosome/FasL into mice with established CIA resulted in significant disease amelioration. These results demonstrate that both systemic and local administration of exosomes derived from FasL-expressing DC are able to suppress antigen-specific immune responses through an MHC class II-dependent pathway, resulting in effective and sustained treatment of established collagen-induced arthritis and suppression of the DTH inflammatory response. These results suggest that DC/FasL-derived exosomes could be used clinically for the treatment of inflammatory and autoimmune diseases.
Prevention of type 1 diabetes: today and tomorrow (2010)

The aim of therapeutic interventions for type 1 diabetes is to suppress pathogenic autoreactivity and to preserve/restore beta-cell mass and function to physiologically sufficient levels to maintain good metabolic control. During the natural history of type 1 diabetes, several strategies have been applied at various stages in the form of primary, secondary or tertiary prevention approaches. Clinical trials using antigen-specific (e.g. DiaPep277, human glutamic acid decarboxylase 65 (GAD65)) or non-specific immune therapies (e.g. anti-CD3 monoclonal antibodies) have shown some benefit in the modulation of the autoimmune process and prevention of the insulin secretion loss in the short term after diagnosis of diabetes. A single long-term effective therapy has not been identified yet, and it is likely that in most cases a rationally designed combinatorial approach using immunotherapeutic methods coupled with islet regeneration or replacement will prove to be most effective.
Paclitaxel Resistance in Non–Small-Cell Lung Cancer Associated With Beta-Tubulin Gene Mutations (1999)

We have identified beta-tubulin gene mutations as a strong predictor of response to the antitubulin drug paclitaxel; these mutations may represent a novel mechanism of resistance and should be examined prospectively in future trials of taxane-based therapy in NSCLC.
Monoclonal and recombinant antibodies, 30 years after … (2006)

In 1975, the hybridoma technology provided, for the first time, an access to murine monoclonal antibodies. During the two following decades, their high potential, as laboratory tools, was rapidly exploited, but in vivo applications were still very limited. Nowadays, antibodies, omnipresent in both diagnostic and research domains, are largely invading the domain of therapy. A wide array of novel technologies, including phage display and transgenic mice, to isolate fully human antibodies and engineer these molecules, has been implemented. The natural propensity, of the antibody molecules, to metamorphosis makes them an ideal response to new applications and therapeutic challenges. The present review is a tentative update of the different antibody "formats" and a walk through the techniques recently applied to antibody engineering. In addition it also addresses some specific issues such as the development of expression systems suitable for large-scale production of recombinant antibodies.
Synthesis-dependent repair of Cpf1-induced double strand DNA breaks enables targeted gene replacement in rice (2018)

The recently developed CRISPR (clustered regularly interspaced short palindromic repeats)/Cpf1 system expands the range of genome editing and is emerging as an alternative powerful tool for both plant functional genomics and crop improvement. Cpf1-CRISPR RNA (crRNA) produces double strand DNA breaks (DSBs) with long 5'-protruding ends, which may facilitate the pairing and insertion of repair templates through homology-directed repair (HDR) for targeted gene replacement and introduction of the desired DNA elements at specific gene loci for crop improvement. However, the potential mechanism underlying HDR of DSBs generated by Cpf1-crRNA remains to be investigated, and the inherent low efficiency of HDR and poor availability of exogenous donor DNA as repair templates strongly impede the use of HDR for precise genome editing in crop plants. Here, we provide evidence of synthesis-dependent repair of Cpf1-induced DSBs, which enables us precisely to replace the wild-type ALS gene with the intended mutant version that carries two discrete point mutations conferring herbicide resistance to rice plants. Our observation that the donor repair template (DRT) with only the left homologous arm is sufficient for precise targeted allele replacement offers a better understanding of the mechanism underlying HDR in plants, and greatly simplifies the design of DRTs for precision genome editing in crop improvement.
Corroboration of Dahl S Q276L α1Na,K-ATPase protein sequence: impact on affinities for ligands and on E1 conformation (2005)

Data demonstrate the existence and functional significance of the Q276L variant in Dahl S rats.
Low-voltage low-power K-band balanced RTD-based MMIC VCO (2006)

This paper presents a K-band balanced RTD-based MMIC VCO with extremely low power consumption. In order to reduce the power consumption, an InP-based RTD is used for microwave power generation. The K-band VCO generates an RF output power of -17.7 dBm at a DC power of 1.0 mW. A wide tuning range of 2.1 GHz is obtained by using the base-collector junction of the integrated HBT as a varactor. In addition, a low phase noise of -108 dBc/Hz at 1 MHz offset at 22.2 GHz has been obtained
Vaccination with a plasmid DNA encoding HER-2/neu together with low doses of GM-CSF and IL-2 in patients with metastatic breast carcinoma: a pilot clinical trial (2010)

This pilot clinical trial demonstrates that Her2-pDNA vaccination in conjunction with GM-CSF and IL-2 administration is safe, well tolerated and can induce long-lasting cellular and humoral immune responses against Her2 in patients with advanced breast cancer.
Modelling Speech Acts in Conversational Discourse (2005)

Computational pragmatics and dialogue analysis is currently a rapid growing area of research in computational linguistics. Over the past five years or so, initiatives in modelling pragmatic aspects of dialogue have led to considerably improved spoken language dialogue systems ï¿½ so much so in fact that constrained human-computer interaction no longer seems out of the question.&#13;\n&#13;\nOne of the main drawbacks to such systems however is highlighted by the word "constrained". Human communication is seldom confined to answering questions or solving problems within a restricted field (such as train timetable enquiries, or route finding, for instance). How can one tell whether theories of dialogue that work well in domain specific, task-oriented dialogue, can be scaled up or expanded to deal with natural conversation?&#13;\n&#13;\nIn this dissertation I have carried out a critical survey of the various approaches to speech act modelling, detailing what I think are the strengths and weaknesses in the current theories. One very promising approach is that of using speech act analysis as a means of interpreting a speaker's intentions in producing an utterance. This then forms the basis for determining a hearer's response (following certain rules of conversational co-operation). I go on to present what is intended as a preliminary model, which is designed to capture the characteristic relationship and interaction of speech acts in conversational dialogue, especially those features which preceding research has failed to represent. Speech acts are defined by means of schemata that match the state of the prevailing conversational context space. Each possible contexgt space is specified in the model for the performance of a particular speech act or acts; the representation of the context space is then updated accordingly.&#13;\n&#13;\nI illustrate the theoretical model using real conversation, collected during the course of this research, and compare its performance against the analysis of a "benchmark" conversation, highlighting where the model falls short and how it could be improved in the future. I will argue that the model provides a powerful formalism for the characterisation of a wide variety of different basic speech acts.
Taxonomical Description, Nativity and Endemism with Particular Reference to Threatened Ethnomedicinal Plants of Almora District of Western Himalaya (2014)

Out of 187 ethno-medicinal plants of Almora district (Kumari et. al. 2011), identifications, distribution, nativity and endemic/near endemic of 21 threatened ethno-medicinal plant species were studied. These 21 species of ethno medicinal plants belonging to 16 families were recorded. Of these, 2 species were trees, 1 shrub, 16 herbs and 2 climbers. The families Taxaceae, Ranunculaceae, Berberadaceae, Euphorbiaceae, Saxifragaceae,Verbenaceae,Bignonoaceae, Celastraceae, Costaceae, Dioscoreaceae, Hypoxidaceae, Valerianaceae and Gentianaceae having single species,  Lamiaceae, having two species and Orchidaceae, Liliaceae having three species were identified.
In vitro assessments of viscoelastic properties of fibrin clot by using acoustic radiation force on a solid sphere (2010)

In present study, the effect of red blood cells concentration on the clot viscoelastic properties was assessed by acoustic radiation force technique in vitro. The experiments were performed on porcine whole blood with different hematocrits from 0 to 40%. Clot formation was induced by adding 2 ml of 0.5 M CaCl <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> solution into a 20-ml blood sample. The viscoelastic properties of clot were estimated by detecting the displacement of a solid sphere within clot in response to the applied acoustic radiation force. In experimental system, the solid sphere was pushed by a 1 MHz single element focused transducer. Another single element focused transducer with a center frequency of 20 MHz was used to track the displacements of sphere. For each clot sample, acoustic radiation force tone bursts of 0.25 ms to 7 ms are applied in consecutive experiments. The spatio-temporal behavior of the displacement of sphere was used to assess the viscoelastic properties of clot (with different hematocrits). The experimental result indicates that the value of shear modulus of blood clot decreased from 585±127 Pa at plasma to 168±26 Pa at 40% hematocrit. This result can be used to explain that the concentration of fibrinogen plays the major role in clot elastic properties. In addition, the viscoelastic properties of blood clot can be assessed using a temporal behavior rather than a spatial approach.
Biological therapy of ovarian cancer: current directions. (1998)

Despite recent advances in the chemotherapy of ovarian cancer, the development of alternative therapies that retain activity against drug-resistant tumors remains a high priority. Our knowledge regarding growth factors, cytokines, and the immune response continues to expand, and molecular biology has provided an increased diversity of reagents for clinical evaluation. This review focuses on regulatory targets in ovarian cancer, including Her2/neu (c-erbB2) and other growth factor receptors; interferons, interleukins, and other immunoregulatory cytokines; cellular adhesion molecules; antigen-specific T lymphocytes and adoptive immunotherapy; choice of monoclonal antibody reagents and advances in antibody engineering, including recombinant single-chain binding sites, chimeric proteins, radioconjugates, cytotoxic drug conjugates, immunotoxins, and bispecific antibodies. Although specific roles for biologic therapy in the management of ovarian cancer have yet to be defined, current priorities for clinical research are reviewed.
Effects of pendant groups at phosphorus on binding properties of d-ApA analogues (1986)

The interaction of several synthetic analogues of d-ApA with Poly U and Poly dT was examined to explore the effects of substituents at phosphorus on binding properties of oligonucleotides. These analogues contained a bulky, lipophilic group (2,2,2-trichloroethoxy or 2,2,2-trichloro-1,1-dimethylethoxy) a small, uncharged hydrogen-bonding group (amido), or a cationic phosphoramidate (2-aminoethylamido, protonated in neutral aqueous media) in place of the anionic oxygen of the internucleotide phosphate. As determined by "melting curves" each formed a complex with Poly U more stable than the Poly U.d-ApA complex. Binding to Poly dT was comparable or in some cases stronger. Checks on composition (mixing curves) revealed the expected stoichiometry of ldA:2U (or 2dT). Stereochemistry at phosphorus influenced stability of the complexes, but the effect was not a major one. These results suggest that oligonucleotides containing large, lipophilic groups, as well as small non-ionic groups (e.g., the methyl phosphonates) or polar groups, could be useful as probes in hybridization experiments.